PMID- 37414772
OWN - NLM
STAT- MEDLINE
DCOM- 20230711
LR  - 20230711
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Jul 6
TI  - A spatio-temporally constrained gene regulatory network directed by PBX1/2 
      acquires limb patterning specificity via HAND2.
PG  - 3993
LID - 10.1038/s41467-023-39443-z [doi]
LID - 3993
AB  - A lingering question in developmental biology has centered on how transcription 
      factors with widespread distribution in vertebrate embryos can perform 
      tissue-specific functions. Here, using the murine hindlimb as a model, we 
      investigate the elusive mechanisms whereby PBX TALE homeoproteins, viewed 
      primarily as HOX cofactors, attain context-specific developmental roles despite 
      ubiquitous presence in the embryo. We first demonstrate that mesenchymal-specific 
      loss of PBX1/2 or the transcriptional regulator HAND2 generates similar limb 
      phenotypes. By combining tissue-specific and temporally controlled mutagenesis 
      with multi-omics approaches, we reconstruct a gene regulatory network (GRN) at 
      organismal-level resolution that is collaboratively directed by PBX1/2 and HAND2 
      interactions in subsets of posterior hindlimb mesenchymal cells. Genome-wide 
      profiling of PBX1 binding across multiple embryonic tissues further reveals that 
      HAND2 interacts with subsets of PBX-bound regions to regulate limb-specific GRNs. 
      Our research elucidates fundamental principles by which promiscuous transcription 
      factors cooperate with cofactors that display domain-restricted localization to 
      instruct tissue-specific developmental programs.
CI  - © 2023. The Author(s).
FAU - Losa, Marta
AU  - Losa M
AD  - Program in Craniofacial Biology, Institute for Human Genetics, Eli and Edythe 
      Broad Center of Regeneration Medicine and Stem Cell Research, Department of 
      Orofacial Sciences and Department of Anatomy, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Barozzi, Iros
AU  - Barozzi I
AUID- ORCID: 0000-0003-0690-3473
AD  - Center for Cancer Research, Medical University of Vienna, Vienna, Austria.
FAU - Osterwalder, Marco
AU  - Osterwalder M
AUID- ORCID: 0000-0002-1969-2313
AD  - Environmental Genomics and Systems Biology Division, Lawrence Berkeley National 
      Laboratory, Berkeley, CA, USA.
AD  - Department for Biomedical Research (DBMR), University of Bern, Bern, Switzerland.
AD  - Department of Cardiology, Bern University Hospital, Bern, Switzerland.
FAU - Hermosilla-Aguayo, Viviana
AU  - Hermosilla-Aguayo V
AUID- ORCID: 0000-0002-2495-4867
AD  - Program in Craniofacial Biology, Institute for Human Genetics, Eli and Edythe 
      Broad Center of Regeneration Medicine and Stem Cell Research, Department of 
      Orofacial Sciences and Department of Anatomy, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Morabito, Angela
AU  - Morabito A
AD  - Developmental Genetics, Department Biomedicine, University of Basel, Basel, 
      Switzerland.
FAU - Chacón, Brandon H
AU  - Chacón BH
AUID- ORCID: 0000-0002-4776-5946
AD  - Program in Craniofacial Biology, Institute for Human Genetics, Eli and Edythe 
      Broad Center of Regeneration Medicine and Stem Cell Research, Department of 
      Orofacial Sciences and Department of Anatomy, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Zarrineh, Peyman
AU  - Zarrineh P
AD  - School of Medical Sciences, University of Manchester, Manchester, UK.
FAU - Girdziusaite, Ausra
AU  - Girdziusaite A
AD  - Developmental Genetics, Department Biomedicine, University of Basel, Basel, 
      Switzerland.
FAU - Benazet, Jean Denis
AU  - Benazet JD
AD  - Program in Craniofacial Biology, Institute for Human Genetics, Eli and Edythe 
      Broad Center of Regeneration Medicine and Stem Cell Research, Department of 
      Orofacial Sciences and Department of Anatomy, University of California San 
      Francisco, San Francisco, CA, USA.
FAU - Zhu, Jianjian
AU  - Zhu J
AD  - Cancer and Developmental Biology Laboratory, Center for Cancer Research, National 
      Cancer Institute, Frederick, MD, USA.
FAU - Mackem, Susan
AU  - Mackem S
AUID- ORCID: 0000-0002-9095-9914
AD  - Cancer and Developmental Biology Laboratory, Center for Cancer Research, National 
      Cancer Institute, Frederick, MD, USA.
FAU - Capellini, Terence D
AU  - Capellini TD
AUID- ORCID: 0000-0003-3842-8478
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Dickel, Diane
AU  - Dickel D
AUID- ORCID: 0000-0001-5497-6824
AD  - Environmental Genomics and Systems Biology Division, Lawrence Berkeley National 
      Laboratory, Berkeley, CA, USA.
FAU - Bobola, Nicoletta
AU  - Bobola N
AUID- ORCID: 0000-0002-7103-4932
AD  - School of Medical Sciences, University of Manchester, Manchester, UK.
FAU - Zuniga, Aimée
AU  - Zuniga A
AUID- ORCID: 0000-0002-9953-3637
AD  - Developmental Genetics, Department Biomedicine, University of Basel, Basel, 
      Switzerland.
FAU - Visel, Axel
AU  - Visel A
AUID- ORCID: 0000-0002-4130-7784
AD  - Environmental Genomics and Systems Biology Division, Lawrence Berkeley National 
      Laboratory, Berkeley, CA, USA.
AD  - US Department of Energy Joint Genome Institute, Lawrence Berkeley National 
      Laboratory, Berkeley, CA, 94720, USA.
AD  - School of Natural Sciences, University of California, Merced, Merced, CA, 95343, 
      USA.
FAU - Zeller, Rolf
AU  - Zeller R
AUID- ORCID: 0000-0002-3186-7403
AD  - Developmental Genetics, Department Biomedicine, University of Basel, Basel, 
      Switzerland.
FAU - Selleri, Licia
AU  - Selleri L
AUID- ORCID: 0000-0002-6817-1469
AD  - Program in Craniofacial Biology, Institute for Human Genetics, Eli and Edythe 
      Broad Center of Regeneration Medicine and Stem Cell Research, Department of 
      Orofacial Sciences and Department of Anatomy, University of California San 
      Francisco, San Francisco, CA, USA. licia.selleri@ucsf.edu.
LA  - eng
GR  - R01 HG003988/HG/NHGRI NIH HHS/United States
GR  - R01 DE028599/DE/NIDCR NIH HHS/United States
GR  - R01 DE028324/DE/NIDCR NIH HHS/United States
GR  - R01 HD043997/HD/NICHD NIH HHS/United States
GR  - UM1 HG009421/HG/NHGRI NIH HHS/United States
PT  - Journal Article
DEP - 20230706
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Pre-B-Cell Leukemia Transcription Factor 1)
RN  - 0 (Transcription Factors)
RN  - 0 (Pbx1 protein, mouse)
RN  - 0 (Pbx2 protein, mouse)
RN  - 0 (Hand2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Gene Regulatory Networks
MH  - Homeodomain Proteins/metabolism
MH  - Pre-B-Cell Leukemia Transcription Factor 1/genetics
MH  - *Transcription Factors/genetics/metabolism
PMC - PMC10325989
COIS- The authors declare no competing interests.
EDAT- 2023/07/07 01:05
MHDA- 2023/07/10 06:42
CRDT- 2023/07/06 23:16
PHST- 2022/03/17 00:00 [received]
PHST- 2023/06/14 00:00 [accepted]
PHST- 2023/07/10 06:42 [medline]
PHST- 2023/07/07 01:05 [pubmed]
PHST- 2023/07/06 23:16 [entrez]
AID - 10.1038/s41467-023-39443-z [pii]
AID - 39443 [pii]
AID - 10.1038/s41467-023-39443-z [doi]
PST - epublish
SO  - Nat Commun. 2023 Jul 6;14(1):3993. doi: 10.1038/s41467-023-39443-z.

PMID- 37330998
OWN - NLM
STAT- MEDLINE
DCOM- 20230620
LR  - 20230710
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Print)
IS  - 1420-682X (Linking)
VI  - 80
IP  - 7
DP  - 2023 Jun 18
TI  - The Notch-mediated circuitry in the evolution and generation of new cell 
      lineages: the tooth model.
PG  - 182
LID - 10.1007/s00018-023-04831-7 [doi]
LID - 182
AB  - The Notch pathway is an ancient, evolutionary conserved intercellular signaling 
      mechanism that is involved in cell fate specification and proper embryonic 
      development. The Jagged2 gene, which encodes a ligand for the Notch family of 
      receptors, is expressed from the earliest stages of odontogenesis in epithelial 
      cells that will later generate the enamel-producing ameloblasts. Homozygous 
      Jagged2 mutant mice exhibit abnormal tooth morphology and impaired enamel 
      deposition. Enamel composition and structure in mammals are tightly linked to the 
      enamel organ that represents an evolutionary unit formed by distinct dental 
      epithelial cell types. The physical cooperativity between Notch ligands and 
      receptors suggests that Jagged2 deletion could alter the expression profile of 
      Notch receptors, thus modifying the whole Notch signaling cascade in cells within 
      the enamel organ. Indeed, both Notch1 and Notch2 expression are severely 
      disturbed in the enamel organ of Jagged2 mutant teeth. It appears that the 
      deregulation of the Notch signaling cascade reverts the evolutionary path 
      generating dental structures more reminiscent of the enameloid of fishes rather 
      than of mammalian enamel. Loss of interactions between Notch and Jagged proteins 
      may initiate the suppression of complementary dental epithelial cell fates 
      acquired during evolution. We propose that the increased number of Notch 
      homologues in metazoa enabled incipient sister cell types to form and maintain 
      distinctive cell fates within organs and tissues along evolution.
CI  - © 2023. The Author(s).
FAU - Mitsiadis, Thimios A
AU  - Mitsiadis TA
AUID- ORCID: 0000-0002-9812-9982
AD  - Institute of Oral Biology, Centre for Dental Medicine, University of Zurich, 
      Plattenstrasse 11, 8032, Zurich, Switzerland. thimios.mitsiadis@zzm.uzh.ch.
FAU - Pagella, Pierfrancesco
AU  - Pagella P
AD  - Institute of Oral Biology, Centre for Dental Medicine, University of Zurich, 
      Plattenstrasse 11, 8032, Zurich, Switzerland.
AD  - Wallenberg Center for Molecular Medicine (WCMM) and Department of Biomedical and 
      Clinical Sciences, Linköpings Universitet, 581 85, Linköping, Sweden.
FAU - Capellini, Terence D
AU  - Capellini TD
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, 
      02138, USA.
FAU - Smith, Moya Meredith
AU  - Smith MM
AD  - Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, King's 
      College London, London, UK.
LA  - eng
GR  - institutional funds/Universität Zürich/
PT  - Journal Article
DEP - 20230618
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Notch)
RN  - 0 (Serrate-Jagged Proteins)
RN  - 0 (Carrier Proteins)
SB  - IM
MH  - Pregnancy
MH  - Female
MH  - Mice
MH  - Animals
MH  - Cell Lineage/genetics
MH  - *Membrane Proteins/metabolism
MH  - *Receptors, Notch/genetics/metabolism
MH  - Serrate-Jagged Proteins/metabolism
MH  - Cell Differentiation/physiology
MH  - Carrier Proteins
MH  - Mammals/metabolism
PMC - PMC10277265
OTO - NOTNLM
OT  - Ameloblasts
OT  - Cell commitment
OT  - Enamel
OT  - Enamel organ
OT  - Evolution
OT  - Jagged
OT  - Notch signaling
OT  - Tooth development
COIS- The authors declare no conflict of interests.
EDAT- 2023/06/18 19:17
MHDA- 2023/06/20 06:42
CRDT- 2023/06/18 14:49
PHST- 2023/03/14 00:00 [received]
PHST- 2023/06/09 00:00 [accepted]
PHST- 2023/05/19 00:00 [revised]
PHST- 2023/06/20 06:42 [medline]
PHST- 2023/06/18 19:17 [pubmed]
PHST- 2023/06/18 14:49 [entrez]
AID - 10.1007/s00018-023-04831-7 [pii]
AID - 4831 [pii]
AID - 10.1007/s00018-023-04831-7 [doi]
PST - epublish
SO  - Cell Mol Life Sci. 2023 Jun 18;80(7):182. doi: 10.1007/s00018-023-04831-7.

PMID- 37272420
OWN - NLM
STAT- MEDLINE
DCOM- 20230703
LR  - 20230708
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 150
IP  - 13
DP  - 2023 Jul 1
TI  - Molecular mechanism of synovial joint site specification and induction in 
      developing vertebrate limbs.
LID - 10.1242/dev.201335 [doi]
LID - dev201335
AB  - The vertebrate appendage comprises three primary segments, the stylopod, zeugopod 
      and autopod, each separated by joints. The molecular mechanisms governing the 
      specification of joint sites, which define segment lengths and thereby limb 
      architecture, remain largely unknown. Existing literature suggests that 
      reciprocal gradients of retinoic acid (RA) and fibroblast growth factor (FGF) 
      signaling define the expression domains of the putative segment markers Meis1, 
      Hoxa11 and Hoxa13. Barx1 is expressed in the presumptive joint sites. Our data 
      demonstrate that RA-FGF signaling gradients define the expression domain of Barx1 
      in the first presumptive joint site. When misexpressed, Barx1 induces ectopic 
      interzone-like structures, and its loss of function partially blocks interzone 
      development. Simultaneous perturbations of RA-FGF signaling gradients result in 
      predictable shifts of Barx1 expression domains along the proximo-distal axis and, 
      consequently, in the formation of repositioned joints. Our data suggest that 
      during early limb bud development in chick, Meis1 and Hoxa11 expression domains 
      are overlapping, whereas the Barx1 expression domain resides within the Hoxa11 
      expression domain. However, once the interzone is formed, the expression domains 
      are refined and the Barx1 expression domain becomes congruent with the border of 
      these two putative segment markers.
CI  - © 2023. Published by The Company of Biologists Ltd.
FAU - Yadav, Upendra S
AU  - Yadav US
AD  - Department of Biological Sciences and Bioengineering, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
AD  - The Mehta Family Centre for Engineering in Medicine, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
FAU - Biswas, Tathagata
AU  - Biswas T
AUID- ORCID: 0000-0002-4067-3643
AD  - Department of Biological Sciences and Bioengineering, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
AD  - The Mehta Family Centre for Engineering in Medicine, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
FAU - Singh, Pratik N
AU  - Singh PN
AD  - Department of Biological Sciences and Bioengineering, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
AD  - The Mehta Family Centre for Engineering in Medicine, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
FAU - Gupta, Pankaj
AU  - Gupta P
AD  - Department of Biological Sciences and Bioengineering, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
AD  - The Mehta Family Centre for Engineering in Medicine, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
FAU - Chakraborty, Soura
AU  - Chakraborty S
AUID- ORCID: 0000-0002-3653-9652
AD  - Department of Biological Sciences and Bioengineering, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
FAU - Delgado, Irene
AU  - Delgado I
AD  - Cardiovascular Regeneration Program, Centro Nacional de Investigaciones 
      Cardiovasculares, CNIC, 28029 Madrid, Spain.
FAU - Zafar, Hamim
AU  - Zafar H
AUID- ORCID: 0000-0002-1617-2806
AD  - Department of Biological Sciences and Bioengineering, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
AD  - The Mehta Family Centre for Engineering in Medicine, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
AD  - Department of Computer Science and Engineering, Indian Institute of Technology 
      Kanpur, Kanpur, Uttar Pradesh 208016, India.
FAU - Capellini, Terence D
AU  - Capellini TD
AD  - Department of Human Evolutionary Biology, Harvard University, 11 Divinity Avenue, 
      Cambridge, MA 02138, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA.
FAU - Torres, Miguel
AU  - Torres M
AD  - Cardiovascular Regeneration Program, Centro Nacional de Investigaciones 
      Cardiovasculares, CNIC, 28029 Madrid, Spain.
FAU - Bandyopadhyay, Amitabha
AU  - Bandyopadhyay A
AUID- ORCID: 0000-0002-0429-438X
AD  - Department of Biological Sciences and Bioengineering, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
AD  - The Mehta Family Centre for Engineering in Medicine, Indian Institute of 
      Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
LA  - eng
GR  - R01 AR070139/AR/NIAMS NIH HHS/United States
PT  - Journal Article
DEP - 20230630
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Transcription Factors)
RN  - 0 (Myeloid Ecotropic Viral Integration Site 1 Protein)
SB  - IM
MH  - Animals
MH  - *Transcription Factors/genetics/metabolism
MH  - *Joints/metabolism
MH  - Myeloid Ecotropic Viral Integration Site 1 Protein/genetics/metabolism
MH  - Vertebrates/genetics/metabolism
MH  - Extremities
MH  - Gene Expression Regulation, Developmental
PMC - PMC10323242
OTO - NOTNLM
OT  - Barx1
OT  - Cartilage segmentation
OT  - Limb patterning
OT  - RA/FGF signaling
OT  - Synovial joints
COIS- Competing interests The authors declare no competing or financial interests.
EDAT- 2023/06/05 06:42
MHDA- 2023/07/03 06:41
PMCR- 2024/06/30
CRDT- 2023/06/05 05:53
PHST- 2022/09/30 00:00 [received]
PHST- 2023/05/25 00:00 [accepted]
PHST- 2024/06/30 00:00 [pmc-release]
PHST- 2023/07/03 06:41 [medline]
PHST- 2023/06/05 06:42 [pubmed]
PHST- 2023/06/05 05:53 [entrez]
AID - 314422 [pii]
AID - DEV201335 [pii]
AID - 10.1242/dev.201335 [doi]
PST - ppublish
SO  - Development. 2023 Jul 1;150(13):dev201335. doi: 10.1242/dev.201335. Epub 2023 Jun 
      30.

PMID- 37104592
OWN - NLM
STAT- MEDLINE
DCOM- 20230515
LR  - 20230523
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 380
IP  - 6643
DP  - 2023 Apr 28
TI  - The functional and evolutionary impacts of human-specific deletions in conserved 
      elements.
PG  - eabn2253
LID - 10.1126/science.abn2253 [doi]
AB  - Conserved genomic sequences disrupted in humans may underlie uniquely human 
      phenotypic traits. We identified and characterized 10,032 human-specific 
      conserved deletions (hCONDELs). These short (average 2.56 base pairs) deletions 
      are enriched for human brain functions across genetic, epigenomic, and 
      transcriptomic datasets. Using massively parallel reporter assays in six cell 
      types, we discovered 800 hCONDELs conferring significant differences in 
      regulatory activity, half of which enhance rather than disrupt regulatory 
      function. We highlight several hCONDELs with putative human-specific effects on 
      brain development, including HDAC5, CPEB4, and PPP2CA. Reverting an hCONDEL to 
      the ancestral sequence alters the expression of LOXL2 and developmental genes 
      involved in myelination and synaptic function. Our data provide a rich resource 
      to investigate the evolutionary mechanisms driving new traits in humans and other 
      species.
FAU - Xue, James R
AU  - Xue JR
AUID- ORCID: 0000-0002-3332-5747
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Center for System Biology, Department of Organismic and Evolutionary Biology, 
      Harvard University, Cambridge, MA, USA.
FAU - Mackay-Smith, Ava
AU  - Mackay-Smith A
AUID- ORCID: 0000-0003-0404-0563
AD  - Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
FAU - Mouri, Kousuke
AU  - Mouri K
AUID- ORCID: 0000-0003-1712-6833
AD  - The Jackson Laboratory, Bar Harbor, ME, USA.
FAU - Garcia, Meilin Fernandez
AU  - Garcia MF
AUID- ORCID: 0000-0002-8745-9775
AD  - Department of Psychiatry, Yale University, New Haven, CT, USA.
FAU - Dong, Michael X
AU  - Dong MX
AUID- ORCID: 0000-0003-4084-3099
AD  - Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, 
      Uppsala University, Uppsala, Sweden.
FAU - Akers, Jared F
AU  - Akers JF
AUID- ORCID: 0000-0002-9270-0017
AD  - Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
FAU - Noble, Mark
AU  - Noble M
AUID- ORCID: 0000-0002-9618-120X
AD  - Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
FAU - Li, Xue
AU  - Li X
AUID- ORCID: 0000-0002-9126-2692
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Program in Bioinformatics and Integrative Biology, UMass Chan Medical School, 
      Worcester, MA, USA.
AD  - Program in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA.
CN  - Zoonomia Consortium†
FAU - Lindblad-Toh, Kerstin
AU  - Lindblad-Toh K
AUID- ORCID: 0000-0001-8338-0253
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, 
      Uppsala University, Uppsala, Sweden.
FAU - Karlsson, Elinor K
AU  - Karlsson EK
AUID- ORCID: 0000-0002-4343-3776
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Program in Bioinformatics and Integrative Biology, UMass Chan Medical School, 
      Worcester, MA, USA.
AD  - Program in Molecular Medicine, UMass Chan Medical School, Worcester, MA, USA.
FAU - Noonan, James P
AU  - Noonan JP
AUID- ORCID: 0000-0001-9632-5835
AD  - Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
AD  - Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
AD  - Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, 
      USA.
FAU - Capellini, Terence D
AU  - Capellini TD
AUID- ORCID: 0000-0003-3842-8478
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Brennand, Kristen J
AU  - Brennand KJ
AUID- ORCID: 0000-0003-0993-5956
AD  - Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
AD  - Department of Psychiatry, Yale University, New Haven, CT, USA.
FAU - Tewhey, Ryan
AU  - Tewhey R
AUID- ORCID: 0000-0002-4607-8001
AD  - The Jackson Laboratory, Bar Harbor, ME, USA.
AD  - Graduate School of Biomedical Sciences and Engineering, University of Maine, 
      Orono, ME, USA.
AD  - Graduate School of Biomedical Sciences Tufts University School of Medicine, 
      Boston, MA, USA.
FAU - Sabeti, Pardis C
AU  - Sabeti PC
AUID- ORCID: 0000-0002-9843-1890
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Center for System Biology, Department of Organismic and Evolutionary Biology, 
      Harvard University, Cambridge, MA, USA.
AD  - Howard Hughes Medical Institute, Chevy Chase, MD, USA.
AD  - Department of Immunology and Infectious Disease, Harvard T.H. Chan School of 
      Public Health, Boston, MA, USA.
FAU - Reilly, Steven K
AU  - Reilly SK
AUID- ORCID: 0000-0003-3140-1483
AD  - Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
LA  - eng
GR  - K99 HG010669/HG/NHGRI NIH HHS/United States
GR  - R00 HG010669/HG/NHGRI NIH HHS/United States
GR  - R01 HG008742/HG/NHGRI NIH HHS/United States
GR  - R35 HG011329/HG/NHGRI NIH HHS/United States
PT  - Journal Article
DEP - 20230428
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (CPEB4 protein, human)
RN  - 0 (RNA-Binding Proteins)
RN  - EC 3.5.1.98 (HDAC5 protein, human)
RN  - EC 3.1.3.16 (PPP2CA protein, human)
SB  - IM
MH  - Humans
MH  - Conserved Sequence/genetics
MH  - *Evolution, Molecular
MH  - Genome
MH  - Genomics
MH  - RNA-Binding Proteins/genetics
MH  - *Sequence Deletion
MH  - *Brain/growth & development
MH  - *Gene Expression Regulation, Developmental
PMC - PMC10202372
MID - NIHMS1897409
COIS- Competing interests: P.C.S. is a cofounder of and consultant to Sherlock 
      Biosciences and Delve Bio. She is also a board member of Danaher Corporation. She 
      is a shareholder in all three companies. The remaining authors declare no 
      competing interests.
FIR - Wirthlin, Morgan E
IR  - Wirthlin ME
FIR - Xue, James R
IR  - Xue JR
FIR - Zhang, Xiaomeng
IR  - Zhang X
FIR - Andrews, Gregory
IR  - Andrews G
FIR - Armstrong, Joel C
IR  - Armstrong JC
FIR - Bianchi, Matteo
IR  - Bianchi M
FIR - Birren, Bruce W
IR  - Birren BW
FIR - Bredemeyer, Kevin R
IR  - Bredemeyer KR
FIR - Breit, Ana M
IR  - Breit AM
FIR - Christmas, Matthew J
IR  - Christmas MJ
FIR - Clawson, Hiram
IR  - Clawson H
FIR - Damas, Joana
IR  - Damas J
FIR - Di Palma, Federica
IR  - Di Palma F
FIR - Diekhans, Mark
IR  - Diekhans M
FIR - Dong, Michael X
IR  - Dong MX
FIR - Eizirik, Eduardo
IR  - Eizirik E
FIR - Fan, Kaili
IR  - Fan K
FIR - Fanter, Cornelia
IR  - Fanter C
FIR - Foley, Nicole M
IR  - Foley NM
FIR - Forsberg-Nilsson, Karin
IR  - Forsberg-Nilsson K
FIR - Garcia, Carlos J
IR  - Garcia CJ
FIR - Gatesy, John
IR  - Gatesy J
FIR - Gazal, Steven
IR  - Gazal S
FIR - Genereux, Diane P
IR  - Genereux DP
FIR - Goodman, Linda
IR  - Goodman L
FIR - Grimshaw, Jenna
IR  - Grimshaw J
FIR - Halsey, Michaela K
IR  - Halsey MK
FIR - Harris, Andrew J
IR  - Harris AJ
FIR - Hickey, Glenn
IR  - Hickey G
FIR - Hiller, Michael
IR  - Hiller M
FIR - Hindle, Allyson G
IR  - Hindle AG
FIR - Hubley, Robert M
IR  - Hubley RM
FIR - Hughes, Graham M
IR  - Hughes GM
FIR - Johnson, Jeremy
IR  - Johnson J
FIR - Juan, David
IR  - Juan D
FIR - Kaplow, Irene M
IR  - Kaplow IM
FIR - Karlsson, Elinor K
IR  - Karlsson EK
FIR - Keough, Kathleen C
IR  - Keough KC
FIR - Kirilenko, Bogdan
IR  - Kirilenko B
FIR - Koepfli, Klaus-Peter
IR  - Koepfli KP
FIR - Korstian, Jennifer M
IR  - Korstian JM
FIR - Kowalczyk, Amanda
IR  - Kowalczyk A
FIR - Kozyrev, Sergey V
IR  - Kozyrev SV
FIR - Lawler, Alyssa J
IR  - Lawler AJ
FIR - Lawless, Colleen
IR  - Lawless C
FIR - Lehmann, Thomas
IR  - Lehmann T
FIR - Levesque, Danielle L
IR  - Levesque DL
FIR - Lewin, Harris A
IR  - Lewin HA
FIR - Li, Xue
IR  - Li X
FIR - Lind, Abigail
IR  - Lind A
FIR - Lindblad-Toh, Kerstin
IR  - Lindblad-Toh K
FIR - Mackay-Smith, Ava
IR  - Mackay-Smith A
FIR - Marinescu, Voichita D
IR  - Marinescu VD
FIR - Marques-Bonet, Tomas
IR  - Marques-Bonet T
FIR - Mason, Victor C
IR  - Mason VC
FIR - Meadows, Jennifer R S
IR  - Meadows JRS
FIR - Meyer, Wynn K
IR  - Meyer WK
FIR - Moore, Jill E
IR  - Moore JE
FIR - Moreira, Lucas R
IR  - Moreira LR
FIR - Moreno-Santillan, Diana D
IR  - Moreno-Santillan DD
FIR - Morrill, Kathleen M
IR  - Morrill KM
FIR - Muntané, Gerard
IR  - Muntané G
FIR - Murphy, William J
IR  - Murphy WJ
FIR - Navarro, Arcadi
IR  - Navarro A
FIR - Nweeia, Martin
IR  - Nweeia M
FIR - Ortmann, Sylvia
IR  - Ortmann S
FIR - Osmanski, Austin
IR  - Osmanski A
FIR - Paten, Benedict
IR  - Paten B
FIR - Paulat, Nicole S
IR  - Paulat NS
FIR - Pfenning, Andreas R
IR  - Pfenning AR
FIR - Phan, BaDoi N
IR  - Phan BN
FIR - Pollard, Katherine S
IR  - Pollard KS
FIR - Pratt, Henry E
IR  - Pratt HE
FIR - Ray, David A
IR  - Ray DA
FIR - Reilly, Steven K
IR  - Reilly SK
FIR - Rosen, Jeb R
IR  - Rosen JR
FIR - Ruf, Irina
IR  - Ruf I
FIR - Ryan, Louise
IR  - Ryan L
FIR - Ryder, Oliver A
IR  - Ryder OA
FIR - Sabeti, Pardis C
IR  - Sabeti PC
FIR - Schäffer, Daniel E
IR  - Schäffer DE
FIR - Serres, Aitor
IR  - Serres A
FIR - Shapiro, Beth
IR  - Shapiro B
FIR - Smit, Arian F A
IR  - Smit AFA
FIR - Springer, Mark
IR  - Springer M
FIR - Srinivasan, Chaitanya
IR  - Srinivasan C
FIR - Steiner, Cynthia
IR  - Steiner C
FIR - Storer, Jessica M
IR  - Storer JM
FIR - Sullivan, Kevin A M
IR  - Sullivan KAM
FIR - Sullivan, Patrick F
IR  - Sullivan PF
FIR - Sundström, Elisabeth
IR  - Sundström E
FIR - Supple, Megan A
IR  - Supple MA
FIR - Swofford, Ross
IR  - Swofford R
FIR - Talbot, Joy-El
IR  - Talbot JE
FIR - Teeling, Emma
IR  - Teeling E
FIR - Turner-Maier, Jason
IR  - Turner-Maier J
FIR - Valenzuela, Alejandro
IR  - Valenzuela A
FIR - Wagner, Franziska
IR  - Wagner F
FIR - Wallerman, Ola
IR  - Wallerman O
FIR - Wang, Chao
IR  - Wang C
FIR - Wang, Juehan
IR  - Wang J
FIR - Weng, Zhiping
IR  - Weng Z
FIR - Wilder, Aryn P
IR  - Wilder AP
EDAT- 2023/04/27 18:41
MHDA- 2023/05/01 06:42
CRDT- 2023/04/27 14:03
PHST- 2023/05/01 06:42 [medline]
PHST- 2023/04/27 18:41 [pubmed]
PHST- 2023/04/27 14:03 [entrez]
AID - 10.1126/science.abn2253 [doi]
PST - ppublish
SO  - Science. 2023 Apr 28;380(6643):eabn2253. doi: 10.1126/science.abn2253. Epub 2023 
      Apr 28.

PMID- 36971423
OWN - NLM
STAT- MEDLINE
DCOM- 20230515
LR  - 20230522
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 324
IP  - 5
DP  - 2023 May 1
TI  - Epigenetics as a mediator of genetic risk in osteoarthritis: role during 
      development, homeostasis, aging, and disease progression.
PG  - C1078-C1088
LID - 10.1152/ajpcell.00574.2022 [doi]
AB  - The identification of genomic loci that are associated with osteoarthritis (OA) 
      has provided a starting point for understanding how genetic variation activates 
      catabolic processes in the joint. However, genetic variants can only alter gene 
      expression and cellular function when the epigenetic environment is permissive to 
      these effects. In this review, we provide examples of how epigenetic shifts at 
      distinct life stages can alter the risk for OA, which we posit is critical for 
      the proper interpretation of genome-wide association studies (GWAS). During 
      development, intensive work on the growth and differentiation factor 5 (GDF5) 
      locus has revealed the importance of tissue-specific enhancer activity in 
      controlling both joint development and the subsequent risk for OA. During 
      homeostasis in adults, underlying genetic risk factors may help establish 
      beneficial or catabolic "set points" that dictate tissue function, with a strong 
      cumulative effect on OA risk. During aging, methylation changes and the 
      reorganization of chromatin can "unmask" the effects of genetic variants. The 
      destructive function of variants that alter aging would only mediate effects 
      after reproductive competence and thus avoid any evolutionary selection pressure, 
      as consistent with larger frameworks of biological aging and its relationship to 
      disease. A similar "unmasking" may occur during OA progression, which is 
      supported by the finding of distinct expression quantitative trait loci (eQTLs) 
      in chondrocytes depending on the degree of tissue degradation. Finally, we 
      propose that massively parallel reporter assays (MPRAs) will be a valuable tool 
      to test the function of putative OA GWAS variants in chondrocytes from different 
      life stages.
FAU - Richard, Daniel
AU  - Richard D
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, 
      Massachusetts, United States.
FAU - Capellini, Terence D
AU  - Capellini TD
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, 
      Massachusetts, United States.
AD  - Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States.
FAU - Diekman, Brian O
AU  - Diekman BO
AUID- ORCID: 0000-0001-9055-4282
AD  - Joint Department of Biomedical Engineering, University of North Carolina at 
      Chapel Hill, Chapel Hill, and North Carolina State University, Raleigh, North 
      Carolina, United States.
AD  - Thurston Arthritis Research Center, The University of North Carolina at Chapel 
      Hill, Chapel Hill, North Carolina, United States.
LA  - eng
GR  - R21 AR077821/AR/NIAMS NIH HHS/United States
GR  - R01 AR070139/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20230327
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Genetic Predisposition to Disease/genetics
MH  - Genome-Wide Association Study
MH  - Epigenesis, Genetic/genetics
MH  - Aging/genetics
MH  - Homeostasis/genetics
MH  - *Osteoarthritis/genetics
MH  - Risk Factors
MH  - Disease Progression
PMC - PMC10191130
OTO - NOTNLM
OT  - GWAS
OT  - epigenetics
OT  - genetics
OT  - osteoarthritis
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2023/03/28 06:00
MHDA- 2023/05/15 06:42
PMCR- 2024/05/01
CRDT- 2023/03/27 08:52
PHST- 2024/05/01 00:00 [pmc-release]
PHST- 2023/05/15 06:42 [medline]
PHST- 2023/03/28 06:00 [pubmed]
PHST- 2023/03/27 08:52 [entrez]
AID - C-00574-2022 [pii]
AID - 10.1152/ajpcell.00574.2022 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2023 May 1;324(5):C1078-C1088. doi: 
      10.1152/ajpcell.00574.2022. Epub 2023 Mar 27.

PMID- 36931425
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20230523
IS  - 1531-4332 (Electronic)
IS  - 1095-6433 (Linking)
VI  - 281
DP  - 2023 Jul
TI  - Human and African ape myosin heavy chain content and the evolution of hominin 
      skeletal muscle.
PG  - 111415
LID - S1095-6433(23)00048-X [pii]
LID - 10.1016/j.cbpa.2023.111415 [doi]
AB  - Humans are unique among terrestrial mammals in our manner of walking and running, 
      reflecting 7 to 8 Ma of musculoskeletal evolution since diverging with the genus 
      Pan. One component of this is a shift in our skeletal muscle biology towards a 
      predominance of myosin heavy chain (MyHC) I isoforms (i.e. slow fibers) across 
      our pelvis and lower limbs, which distinguishes us from chimpanzees. Here, new 
      MyHC data from 35 pelvis and hind limb muscles of a Western gorilla (Gorilla 
      gorilla) are presented. These data are combined with a similar chimpanzee dataset 
      to assess the MyHC I content of humans in comparison to African apes (chimpanzees 
      and gorillas) and other terrestrial mammals. The responsiveness of human skeletal 
      muscle to behavioral interventions is also compared to the human-African ape 
      differential. Humans are distinct from African apes and among a small group of 
      terrestrial mammals whose pelvis and lower limb muscle is slow fiber dominant, on 
      average. Behavioral interventions, including immobilization, bed rest, 
      spaceflight and exercise, can induce modest decreases and increases in human MyHC 
      I content (i.e. -9.3% to 2.3%, n = 2033 subjects), but these shifts are much 
      smaller than the mean human-African ape differential (i.e. 31%). Taken together, 
      these results indicate muscle fiber content is likely an evolvable trait under 
      selection in the hominin lineage. As such, we highlight potential targets of 
      selection in the genome (e.g. regions that regulate MyHC content) that may play 
      an important role in hominin skeletal muscle evolution.
CI  - Copyright © 2023. Published by Elsevier Inc.
FAU - Queeno, Samantha R
AU  - Queeno SR
AD  - Department of Anthropology, University of Oregon, Eugene, OR 97403, USA. 
      Electronic address: https://twitter.com/SamanthaQueeno.
FAU - Reiser, Peter J
AU  - Reiser PJ
AD  - Division of Biosciences, The Ohio State University College of Dentistry, 
      Columbus, OH 43210, USA.
FAU - Orr, Caley M
AU  - Orr CM
AD  - Department of Cell and Developmental Biology, University of Colorado School of 
      Medicine, Aurora, CO 80045, USA; Department of Anthropology, University of 
      Colorado Denver, Denver, CO 80217, USA.
FAU - Capellini, Terence D
AU  - Capellini TD
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 
      02138, USA. Electronic address: https://twitter.com/TDCapellini.
FAU - Sterner, Kirstin N
AU  - Sterner KN
AD  - Department of Anthropology, University of Oregon, Eugene, OR 97403, USA. 
      Electronic address: https://twitter.com/KNSterner.
FAU - O'Neill, Matthew C
AU  - O'Neill MC
AD  - Department of Anatomy, Midwestern University, Glendale, AZ 85309, USA. Electronic 
      address: moneill@midwestern.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20230315
PL  - United States
TA  - Comp Biochem Physiol A Mol Integr Physiol
JT  - Comparative biochemistry and physiology. Part A, Molecular & integrative 
      physiology
JID - 9806096
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
RN  - 0 (Protein Isoforms)
SB  - IM
MH  - Humans
MH  - Animals
MH  - *Myosin Heavy Chains/genetics
MH  - *Hominidae
MH  - Pan troglodytes
MH  - Muscle, Skeletal
MH  - Muscle Fibers, Skeletal
MH  - Protein Isoforms
MH  - Mammals
OTO - NOTNLM
OT  - Chimpanzee
OT  - Enhancers
OT  - Fiber type
OT  - Gorilla
OT  - Hind limb
OT  - Lower limb
OT  - Myosin heavy chain I
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/03/18 06:00
MHDA- 2023/05/22 06:42
CRDT- 2023/03/17 20:29
PHST- 2023/01/09 00:00 [received]
PHST- 2023/03/13 00:00 [revised]
PHST- 2023/03/13 00:00 [accepted]
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/03/18 06:00 [pubmed]
PHST- 2023/03/17 20:29 [entrez]
AID - S1095-6433(23)00048-X [pii]
AID - 10.1016/j.cbpa.2023.111415 [doi]
PST - ppublish
SO  - Comp Biochem Physiol A Mol Integr Physiol. 2023 Jul;281:111415. doi: 
      10.1016/j.cbpa.2023.111415. Epub 2023 Mar 15.

PMID- 36920035
OWN - NLM
STAT- MEDLINE
DCOM- 20230404
LR  - 20230405
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 12
DP  - 2023 Mar 15
TI  - Lineage-specific differences and regulatory networks governing human chondrocyte 
      development.
LID - 10.7554/eLife.79925 [doi]
LID - e79925
AB  - To address large gaps in our understanding of the molecular regulation of 
      articular and growth plate cartilage development in humans, we used our directed 
      differentiation approach to generate these distinct cartilage tissues from human 
      embryonic stem cells. The resulting transcriptomic profiles of hESC-derived 
      articular and growth plate chondrocytes were similar to fetal epiphyseal and 
      growth plate chondrocytes, with respect to genes both known and previously 
      unknown to cartilage biology. With the goal to characterize the regulatory 
      landscapes accompanying these respective transcriptomes, we mapped chromatin 
      accessibility in hESC-derived chondrocyte lineages, and mouse embryonic 
      chondrocytes, using ATAC-sequencing. Integration of the expression dataset with 
      the differentially accessible genomic regions revealed lineage-specific gene 
      regulatory networks. We validated functional interactions of two transcription 
      factors (TFs) (RUNX2 in growth plate chondrocytes and RELA in articular 
      chondrocytes) with their predicted genomic targets. The maps we provide thus 
      represent a framework for probing regulatory interactions governing chondrocyte 
      differentiation. This work constitutes a substantial step towards comprehensive 
      and comparative molecular characterizations of distinct chondrogenic lineages and 
      sheds new light on human cartilage development and biology.
CI  - © 2023, Richard, Pregizer et al.
FAU - Richard, Daniel
AU  - Richard D
AUID- ORCID: 0000-0001-8568-9473
AD  - Human Evolutionary Biology, Harvard University, Cambridge, United States.
FAU - Pregizer, Steven
AU  - Pregizer S
AD  - Department of Orthopedic Research, Boston Children's Hospital, Boston, United 
      States.
AD  - Department of Orthopedic Surgery, Harvard Medical School, Boston, United States.
FAU - Venkatasubramanian, Divya
AU  - Venkatasubramanian D
AD  - Department of Orthopedic Research, Boston Children's Hospital, Boston, United 
      States.
AD  - Department of Orthopedic Surgery, Harvard Medical School, Boston, United States.
AD  - Department of Molecular and Cellular Biology, Harvard University, Cambridge, 
      United States.
FAU - Raftery, Rosanne M
AU  - Raftery RM
AD  - Department of Orthopedic Research, Boston Children's Hospital, Boston, United 
      States.
AD  - Department of Orthopedic Surgery, Harvard Medical School, Boston, United States.
FAU - Muthuirulan, Pushpanathan
AU  - Muthuirulan P
AD  - Human Evolutionary Biology, Harvard University, Cambridge, United States.
FAU - Liu, Zun
AU  - Liu Z
AD  - Human Evolutionary Biology, Harvard University, Cambridge, United States.
FAU - Capellini, Terence D
AU  - Capellini TD
AD  - Human Evolutionary Biology, Harvard University, Cambridge, United States.
AD  - Broad Institute of MIT and Harvard, Cambridge, United States.
FAU - Craft, April M
AU  - Craft AM
AUID- ORCID: 0000-0002-4423-8008
AD  - Department of Orthopedic Research, Boston Children's Hospital, Boston, United 
      States.
AD  - Department of Orthopedic Surgery, Harvard Medical School, Boston, United States.
AD  - Harvard Stem Cell Institute, Cambridge, United States.
LA  - eng
SI  - GEO/GSE195688
SI  - GEO/GSE122877
GR  - R01-AR073821/AR/NIAMS NIH HHS/United States
GR  - R01-AR070139/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230315
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Transcription Factors)
SB  - IM
UOF - doi: 10.1101/2022.05.25.493388
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *Chondrocytes/metabolism
MH  - *Cartilage
MH  - Cell Differentiation/genetics
MH  - Growth Plate
MH  - Transcription Factors/genetics/metabolism
MH  - Chondrogenesis/genetics
PMC - PMC10069868
OTO - NOTNLM
OT  - articular cartilage
OT  - developmental biology
OT  - embryonic stem cells
OT  - epigenetics
OT  - growth plate cartilage
OT  - human
OT  - mouse
OT  - regenerative medicine
OT  - stem cells
OT  - transcription factors
COIS- DR, SP, DV, RR, PM, ZL, TC, AC No competing interests declared
EDAT- 2023/03/16 06:00
MHDA- 2023/04/04 06:42
CRDT- 2023/03/15 08:54
PHST- 2022/05/03 00:00 [received]
PHST- 2023/03/14 00:00 [accepted]
PHST- 2023/04/04 06:42 [medline]
PHST- 2023/03/16 06:00 [pubmed]
PHST- 2023/03/15 08:54 [entrez]
AID - 79925 [pii]
AID - 10.7554/eLife.79925 [doi]
PST - epublish
SO  - Elife. 2023 Mar 15;12:e79925. doi: 10.7554/eLife.79925.

PMID- 36763080
OWN - NLM
STAT- MEDLINE
DCOM- 20230214
LR  - 20230222
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 12
DP  - 2023 Feb 10
TI  - Regulatory dissection of the severe COVID-19 risk locus introgressed by 
      Neanderthals.
LID - 10.7554/eLife.71235 [doi]
LID - e71235
AB  - Individuals infected with the SARS-CoV-2 virus present with a wide variety of 
      symptoms ranging from asymptomatic to severe and even lethal outcomes. Past 
      research has revealed a genetic haplotype on chromosome 3 that entered the human 
      population via introgression from Neanderthals as the strongest genetic risk 
      factor for the severe response to COVID-19. However, the specific variants along 
      this introgressed haplotype that contribute to this risk and the biological 
      mechanisms that are involved remain unclear. Here, we assess the variants present 
      on the risk haplotype for their likelihood of driving the genetic predisposition 
      to severe COVID-19 outcomes. We do this by first exploring their impact on the 
      regulation of genes involved in COVID-19 infection using a variety of population 
      genetics and functional genomics tools. We then perform a locus-specific 
      massively parallel reporter assay to individually assess the regulatory potential 
      of each allele on the haplotype in a multipotent immune-related cell line. We 
      ultimately reduce the set of over 600 linked genetic variants to identify four 
      introgressed alleles that are strong functional candidates for driving the 
      association between this locus and severe COVID-19. Using reporter assays in the 
      presence/absence of SARS-CoV-2, we find evidence that these variants respond to 
      viral infection. These variants likely drive the locus' impact on severity by 
      modulating the regulation of two critical chemokine receptor genes: CCR1 and 
      CCR5. These alleles are ideal targets for future functional investigations into 
      the interaction between host genomics and COVID-19 outcomes.
CI  - © 2023, Jagoda, Marnetto et al.
FAU - Jagoda, Evelyn
AU  - Jagoda E
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, United 
      States.
FAU - Marnetto, Davide
AU  - Marnetto D
AD  - Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu, Estonia.
FAU - Senevirathne, Gayani
AU  - Senevirathne G
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, United 
      States.
FAU - Gonzalez, Victoria
AU  - Gonzalez V
AD  - Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, 
      Canada.
AD  - Vaccine and Infectious Disease Organization, University of Saskatchewan, 
      Saskatoon, Canada.
FAU - Baid, Kaushal
AU  - Baid K
AD  - Vaccine and Infectious Disease Organization, University of Saskatchewan, 
      Saskatoon, Canada.
FAU - Montinaro, Francesco
AU  - Montinaro F
AD  - Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu, Estonia.
AD  - Department of Biology, University of Bari, Bari, Italy.
FAU - Richard, Daniel
AU  - Richard D
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, United 
      States.
FAU - Falzarano, Darryl
AU  - Falzarano D
AD  - Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, 
      Canada.
AD  - Vaccine and Infectious Disease Organization, University of Saskatchewan, 
      Saskatoon, Canada.
FAU - LeBlanc, Emmanuelle V
AU  - LeBlanc EV
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Canada.
FAU - Colpitts, Che C
AU  - Colpitts CC
AUID- ORCID: 0000-0003-2474-1834
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Canada.
FAU - Banerjee, Arinjay
AU  - Banerjee A
AUID- ORCID: 0000-0002-2821-8357
AD  - Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, 
      Canada.
AD  - Vaccine and Infectious Disease Organization, University of Saskatchewan, 
      Saskatoon, Canada.
AD  - Department of Biology, University of Waterloo, Waterloo, Canada.
AD  - Department of Laboratory Medicine and Pathobiology, University of Toronto, 
      Toronto, Canada.
FAU - Pagani, Luca
AU  - Pagani L
AD  - Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu, Estonia.
AD  - Department of Biology, University of Padova, Padova, Italy.
FAU - Capellini, Terence D
AU  - Capellini TD
AUID- ORCID: 0000-0003-3842-8478
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, United 
      States.
AD  - Broad Institute of MIT and Harvard, Cambridge, United States.
LA  - eng
SI  - GEO/GSE176233
GR  - CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20230210
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
SB  - IM
MH  - Humans
MH  - Animals
MH  - *COVID-19/genetics
MH  - *Neanderthals/genetics
MH  - SARS-CoV-2/genetics
MH  - *Virus Diseases
MH  - Genetics, Population
PMC - PMC9917435
OTO - NOTNLM
OT  - CCR1
OT  - CCR5
OT  - COVID-19
OT  - MPRA
OT  - Neandertal introgression
OT  - cis-regulation
OT  - evolutionary biology
OT  - genetics
OT  - genomics
OT  - human
COIS- EJ, DM, GS, VG, KB, FM, DR, DF, EL, CC, AB, LP, TC No competing interests 
      declared
EDAT- 2023/02/11 06:00
MHDA- 2023/02/15 06:00
CRDT- 2023/02/10 10:52
PHST- 2021/06/12 00:00 [received]
PHST- 2023/01/26 00:00 [accepted]
PHST- 2023/02/10 10:52 [entrez]
PHST- 2023/02/11 06:00 [pubmed]
PHST- 2023/02/15 06:00 [medline]
AID - 71235 [pii]
AID - 10.7554/eLife.71235 [doi]
PST - epublish
SO  - Elife. 2023 Feb 10;12:e71235. doi: 10.7554/eLife.71235.

PMID- 35977020
OWN - NLM
STAT- MEDLINE
DCOM- 20220819
LR  - 20230331
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 8
IP  - 33
DP  - 2022 Aug 19
TI  - The developmental impacts of natural selection on human pelvic morphology.
PG  - eabq4884
LID - 10.1126/sciadv.abq4884 [doi]
LID - eabq4884
AB  - Evolutionary responses to selection for bipedalism and childbirth have shaped the 
      human pelvis, a structure that differs substantially from that in apes. 
      Morphology related to these factors is present by birth, yet the 
      developmental-genetic mechanisms governing pelvic shape remain largely unknown. 
      Here, we pinpoint and characterize a key gestational window when human-specific 
      pelvic morphology becomes recognizable, as the ilium and the entire pelvis 
      acquire traits essential for human walking and birth. We next use functional 
      genomics to molecularly characterize chondrocytes from different pelvic 
      subelements during this window to reveal their developmental-genetic 
      architectures. We then find notable evidence of ancient selection and genetic 
      constraint on regulatory sequences involved in ilium expansion and growth, 
      findings complemented by our phenotypic analyses showing that variation in iliac 
      traits is reduced in humans compared to African apes. Our datasets provide 
      important resources for musculoskeletal biology and begin to elucidate 
      developmental mechanisms that shape human-specific morphology.
FAU - Young, Mariel
AU  - Young M
AUID- ORCID: 0000-0001-8931-3588
AD  - Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Richard, Daniel
AU  - Richard D
AUID- ORCID: 0000-0001-8568-9473
AD  - Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Grabowski, Mark
AU  - Grabowski M
AUID- ORCID: 0000-0001-7045-9472
AD  - Research Centre in Evolutionary Anthropology and Palaeoecology, Liverpool John 
      Moores University, Liverpool L3 3AF, UK.
AD  - Department of Biosciences, Centre for Ecological and Evolutionary Synthesis 
      (CEES), University of Oslo, Oslo, Norway.
FAU - Auerbach, Benjamin M
AU  - Auerbach BM
AUID- ORCID: 0000-0002-3435-4427
AD  - Department of Anthropology, The University of Tennessee, Knoxville, TN, USA.
AD  - Department of Ecology and Evolutionary Biology, The University of Tennessee, 
      Knoxville, TN, USA.
FAU - de Bakker, Bernadette S
AU  - de Bakker BS
AUID- ORCID: 0000-0003-0758-4064
AD  - Department of Obstetrics and Gynecology, Amsterdam UMC, University of Amsterdam, 
      Meibergdreef 9, Amsterdam, Netherlands.
AD  - Amsterdam Reproduction and Development Research Institute, Amsterdam, 
      Netherlands.
FAU - Hagoort, Jaco
AU  - Hagoort J
AUID- ORCID: 0000-0002-8324-5390
AD  - Department of Medical Biology, Amsterdam UMC, University of Amsterdam, 
      Meibergdreef 9, Amsterdam, Netherlands.
FAU - Muthuirulan, Pushpanathan
AU  - Muthuirulan P
AUID- ORCID: 0000-0001-6240-3073
AD  - Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Kharkar, Vismaya
AU  - Kharkar V
AUID- ORCID: 0000-0001-5090-7485
AD  - Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Kurki, Helen K
AU  - Kurki HK
AUID- ORCID: 0000-0001-9789-6584
AD  - Department of Anthropology, University of Victoria, STN CSC, Victoria, BC V8W 
      2Y2, Canada.
FAU - Betti, Lia
AU  - Betti L
AUID- ORCID: 0000-0003-2895-9718
AD  - School of Life and Health Sciences, University of Roehampton, London SW15 4JD, 
      UK.
FAU - Birkenstock, Lyena
AU  - Birkenstock L
AUID- ORCID: 0000-0002-1600-6832
AD  - Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Lewton, Kristi L
AU  - Lewton KL
AUID- ORCID: 0000-0003-0674-2454
AD  - Department of Integrative Anatomical Sciences, Keck School of Medicine, 
      University of Southern California, Los Angeles, CA, USA.
FAU - Capellini, Terence D
AU  - Capellini TD
AUID- ORCID: 0000-0003-3842-8478
AD  - Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
LA  - eng
PT  - Journal Article
DEP - 20220817
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
SB  - IM
MH  - Animals
MH  - Biological Evolution
MH  - Female
MH  - *Hominidae/anatomy & histology
MH  - Humans
MH  - Parturition
MH  - *Pelvis/anatomy & histology
MH  - Pregnancy
MH  - Selection, Genetic
PMC - PMC9385149
EDAT- 2022/08/18 06:00
MHDA- 2022/08/20 06:00
CRDT- 2022/08/17 14:04
PHST- 2022/08/17 14:04 [entrez]
PHST- 2022/08/18 06:00 [pubmed]
PHST- 2022/08/20 06:00 [medline]
AID - abq4884 [pii]
AID - 10.1126/sciadv.abq4884 [doi]
PST - ppublish
SO  - Sci Adv. 2022 Aug 19;8(33):eabq4884. doi: 10.1126/sciadv.abq4884. Epub 2022 Aug 
      17.

PMID- 35756893
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 25
IP  - 7
DP  - 2022 Jul 15
TI  - Intronic regulation of SARS-CoV-2 receptor (ACE2) expression mediated by immune 
      signaling and oxidative stress pathways.
PG  - 104614
LID - 10.1016/j.isci.2022.104614 [doi]
LID - 104614
AB  - The angiotensin-converting enzyme 2 (ACE2) protein is a key catalytic regulator 
      of the renin-angiotensin system (RAS), involved in fluid homeostasis and blood 
      pressure modulation. ACE2 also serves as a cell-surface receptor for some 
      coronaviruses such as SARS-CoV and SARS-CoV-2. Improved characterization of ACE2 
      regulation may help us understand the effects of pre-existing conditions on 
      COVID-19 incidence, as well as pathogenic dysregulation following viral 
      infection. Here, we perform bioinformatic analyses to hypothesize on ACE2 gene 
      regulation in two different physiological contexts, identifying putative 
      regulatory elements of ACE2 expression. We perform functional validation of our 
      computational predictions via targeted CRISPR-Cas9 deletions of these elements 
      in vitro, finding them responsive to immune signaling and oxidative-stress 
      pathways. This contributes to our understanding of ACE2 gene regulation at 
      baseline and immune challenge. Our work supports pursuit of these putative 
      mechanisms in our understanding of infection/disease caused by current, and 
      future, SARS-related viruses such as SARS-CoV-2.
CI  - © 2022 The Author(s).
FAU - Richard, Daniel
AU  - Richard D
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 
      02138, USA.
FAU - Muthuirulan, Pushpanathan
AU  - Muthuirulan P
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 
      02138, USA.
FAU - Aguiar, Jennifer
AU  - Aguiar J
AD  - Department of Biology, University of Waterloo, Waterloo, ON N2L3G1, Canada.
FAU - Doxey, Andrew C
AU  - Doxey AC
AD  - Department of Biology, University of Waterloo, Waterloo, ON N2L3G1, Canada.
FAU - Banerjee, Arinjay
AU  - Banerjee A
AD  - Department of Biology, University of Waterloo, Waterloo, ON N2L3G1, Canada.
AD  - Vaccine and Infectious Disease Organization, University of Saskatchewan, 
      Saskatoon, SK S7N 5E3, Canada.
AD  - Department of Veterinary Microbiology, Western College of Veterinary Medicine, 
      University of Saskatchewan, Saskatoon, SK S7N5B4, Canada.
FAU - Mossman, Karen
AU  - Mossman K
AD  - Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
FAU - Hirota, Jeremy
AU  - Hirota J
AD  - Department of Biology, University of Waterloo, Waterloo, ON N2L3G1, Canada.
AD  - Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
AD  - Division of Respiratory Medicine, Department of Medicine, University of British 
      Columbia, Vancouver, BC V5Z 1M9, Canada.
FAU - Capellini, Terence D
AU  - Capellini TD
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 
      02138, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, 02142 MA, USA.
LA  - eng
PT  - Journal Article
DEP - 20220615
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC9213013
OTO - NOTNLM
OT  - Biological sciences
OT  - Immunology
OT  - Molecular biology
OT  - Virology
COIS- The authors declare no competing interests.
EDAT- 2022/06/28 06:00
MHDA- 2022/06/28 06:01
CRDT- 2022/06/27 04:13
PHST- 2021/06/30 00:00 [received]
PHST- 2022/03/19 00:00 [revised]
PHST- 2022/06/10 00:00 [accepted]
PHST- 2022/06/28 06:00 [pubmed]
PHST- 2022/06/28 06:01 [medline]
PHST- 2022/06/27 04:13 [entrez]
AID - S2589-0042(22)00886-0 [pii]
AID - 104614 [pii]
AID - 10.1016/j.isci.2022.104614 [doi]
PST - ppublish
SO  - iScience. 2022 Jul 15;25(7):104614. doi: 10.1016/j.isci.2022.104614. Epub 2022 
      Jun 15.

PMID- 35087045
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220208
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 13
IP  - 1
DP  - 2022 Jan 27
TI  - Author Correction: Joint disease-specificity at the regulatory base-pair level.
PG  - 631
LID - 10.1038/s41467-022-28073-6 [doi]
LID - 631
FAU - Muthuirulan, Pushpanathan
AU  - Muthuirulan P
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Zhao, Dewei
AU  - Zhao D
AD  - Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, 
      Dalian, China.
FAU - Young, Mariel
AU  - Young M
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Richard, Daniel
AU  - Richard D
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Liu, Zun
AU  - Liu Z
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Emami, Alireza
AU  - Emami A
AD  - Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical 
      School, Boston, MA, USA.
FAU - Portilla, Gabriela
AU  - Portilla G
AD  - Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical 
      School, Boston, MA, USA.
FAU - Hosseinzadeh, Shayan
AU  - Hosseinzadeh S
AUID- ORCID: 0000-0002-5326-6852
AD  - Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical 
      School, Boston, MA, USA.
FAU - Cao, Jiaxue
AU  - Cao J
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Maridas, David
AU  - Maridas D
AD  - Department of Developmental Biology, Harvard School of Dental Medicine, Boston, 
      MA, USA.
FAU - Sedlak, Mary
AU  - Sedlak M
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Menghini, Danilo
AU  - Menghini D
AD  - Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical 
      School, Boston, MA, USA.
FAU - Cheng, Liangliang
AU  - Cheng L
AD  - Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, 
      Dalian, China.
FAU - Li, Lu
AU  - Li L
AD  - Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, 
      Dalian, China.
FAU - Ding, Xinjia
AU  - Ding X
AD  - Department of Surgery, the Second Affiliated Hospital of Dalian Medical 
      University, Dalian, China.
FAU - Ding, Yan
AU  - Ding Y
AUID- ORCID: 0000-0002-7708-4391
AD  - Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Rosen, Vicki
AU  - Rosen V
AUID- ORCID: 0000-0002-4029-1055
AD  - Department of Developmental Biology, Harvard School of Dental Medicine, Boston, 
      MA, USA.
FAU - Kiapour, Ata M
AU  - Kiapour AM
AUID- ORCID: 0000-0001-7742-5769
AD  - Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical 
      School, Boston, MA, USA. ata.kiapour@childrens.harvard.edu.
FAU - Capellini, Terence D
AU  - Capellini TD
AUID- ORCID: 0000-0003-3842-8478
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA. 
      tcapellini@fas.harvard.edu.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA. 
      tcapellini@fas.harvard.edu.
LA  - eng
PT  - Published Erratum
DEP - 20220127
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
SB  - IM
EFR - Nat Commun. 2021 Jul 6;12(1):4161. PMID: 34230488
PMC - PMC8795271
EDAT- 2022/01/29 06:00
MHDA- 2022/01/29 06:01
CRDT- 2022/01/28 05:51
PHST- 2022/01/28 05:51 [entrez]
PHST- 2022/01/29 06:00 [pubmed]
PHST- 2022/01/29 06:01 [medline]
AID - 10.1038/s41467-022-28073-6 [pii]
AID - 28073 [pii]
AID - 10.1038/s41467-022-28073-6 [doi]
PST - epublish
SO  - Nat Commun. 2022 Jan 27;13(1):631. doi: 10.1038/s41467-022-28073-6.

PMID- 34793695
OWN - NLM
STAT- MEDLINE
DCOM- 20220411
LR  - 20230125
IS  - 1879-0445 (Electronic)
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 32
IP  - 2
DP  - 2022 Jan 24
TI  - Interspecies transcriptomics identify genes that underlie disproportionate foot 
      growth in jerboas.
PG  - 289-303.e6
LID - S0960-9822(21)01507-4 [pii]
LID - 10.1016/j.cub.2021.10.063 [doi]
AB  - Despite the great diversity of vertebrate limb proportion and our deep 
      understanding of the genetic mechanisms that drive skeletal elongation, little is 
      known about how individual bones reach different lengths in any species. Here, we 
      directly compare the transcriptomes of homologous growth cartilages of the mouse 
      (Mus musculus) and bipedal jerboa (Jaculus jaculus), the latter of which has 
      "mouse-like" arms but extremely long metatarsals of the feet. Intersecting 
      gene-expression differences in metatarsals and forearms of the two species 
      revealed that about 10% of orthologous genes are associated with the 
      disproportionately rapid elongation of neonatal jerboa feet. These include genes 
      and enriched pathways not previously associated with endochondral elongation as 
      well as those that might diversify skeletal proportion in addition to their known 
      requirements for bone growth throughout the skeleton. We also identified 
      transcription regulators that might act as "nodes" for sweeping differences in 
      genome expression between species. Among these, Shox2, which is necessary for 
      proximal limb elongation, has gained expression in jerboa metatarsals where it 
      has not been detected in other vertebrates. We show that Shox2 is sufficient to 
      increase mouse distal limb length, and a nearby putative cis-regulatory region is 
      preferentially accessible in jerboa metatarsals. In addition to mechanisms that 
      might directly promote growth, we found evidence that jerboa foot elongation may 
      occur in part by de-repressing latent growth potential. The genes and pathways 
      that we identified here provide a framework to understand the modular genetic 
      control of skeletal growth and the remarkable malleability of vertebrate limb 
      proportion.
CI  - Copyright © 2021 Elsevier Inc. All rights reserved.
FAU - Saxena, Aditya
AU  - Saxena A
AD  - Division of Biological Sciences, Section of Cell and Developmental Biology, 
      University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
FAU - Sharma, Virag
AU  - Sharma V
AD  - Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 
      108, Dresden 01307, Germany; Max Planck Institute for the Physics of Complex 
      Systems, Nothnitzerstraße 38, Dresden 01187, Germany.
FAU - Muthuirulan, Pushpanathan
AU  - Muthuirulan P
AD  - Department of Human Evolutionary Biology, Harvard University, 11 Divinity Avenue, 
      Cambridge, MA 02138, USA.
FAU - Neufeld, Stanley J
AU  - Neufeld SJ
AD  - Department of Biological Sciences, University of Calgary, 2500 University Drive 
      NW, Calgary, AB T2N 1N4, Canada.
FAU - Tran, Mai P
AU  - Tran MP
AD  - Division of Biological Sciences, Section of Cell and Developmental Biology, 
      University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
FAU - Gutierrez, Haydee L
AU  - Gutierrez HL
AD  - Division of Biological Sciences, Section of Cell and Developmental Biology, 
      University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
FAU - Chen, Kevin D
AU  - Chen KD
AD  - Division of Biological Sciences, Section of Cell and Developmental Biology, 
      University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
FAU - Erberich, Joel M
AU  - Erberich JM
AD  - Division of Biological Sciences, Section of Cell and Developmental Biology, 
      University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
FAU - Birmingham, Amanda
AU  - Birmingham A
AD  - Center for Computational Biology and Bioinformatics, University of California, 
      San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
FAU - Capellini, Terence D
AU  - Capellini TD
AD  - Department of Human Evolutionary Biology, Harvard University, 11 Divinity Avenue, 
      Cambridge, MA 02138, USA.
FAU - Cobb, John
AU  - Cobb J
AD  - Department of Biological Sciences, University of Calgary, 2500 University Drive 
      NW, Calgary, AB T2N 1N4, Canada.
FAU - Hiller, Michael
AU  - Hiller M
AD  - Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 
      108, Dresden 01307, Germany; Max Planck Institute for the Physics of Complex 
      Systems, Nothnitzerstraße 38, Dresden 01187, Germany.
FAU - Cooper, Kimberly L
AU  - Cooper KL
AD  - Division of Biological Sciences, Section of Cell and Developmental Biology, 
      University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. 
      Electronic address: kcooper@ucsd.edu.
LA  - eng
GR  - R01 AR075415/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211117
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Extremities
MH  - Foot
MH  - Mice
MH  - *Rodentia
MH  - Transcription Factors/metabolism
MH  - *Transcriptome
PMC - PMC8792248
MID - NIHMS1758283
OTO - NOTNLM
OT  - evolution of development
OT  - limb development
OT  - skeletal growth
OT  - skeletal proportion
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2021/11/19 06:00
MHDA- 2022/04/12 06:00
CRDT- 2021/11/18 20:10
PHST- 2021/01/07 00:00 [received]
PHST- 2021/07/16 00:00 [revised]
PHST- 2021/10/28 00:00 [accepted]
PHST- 2021/11/19 06:00 [pubmed]
PHST- 2022/04/12 06:00 [medline]
PHST- 2021/11/18 20:10 [entrez]
AID - S0960-9822(21)01507-4 [pii]
AID - 10.1016/j.cub.2021.10.063 [doi]
PST - ppublish
SO  - Curr Biol. 2022 Jan 24;32(2):289-303.e6. doi: 10.1016/j.cub.2021.10.063. Epub 
      2021 Nov 17.

PMID- 34662402
OWN - NLM
STAT- MEDLINE
DCOM- 20220127
LR  - 20220716
IS  - 1537-1719 (Electronic)
IS  - 0737-4038 (Print)
IS  - 0737-4038 (Linking)
VI  - 39
IP  - 1
DP  - 2022 Jan 7
TI  - Detection of Neanderthal Adaptively Introgressed Genetic Variants That Modulate 
      Reporter Gene Expression in Human Immune Cells.
LID - 10.1093/molbev/msab304 [doi]
LID - msab304
AB  - Although some variation introgressed from Neanderthals has undergone selective 
      sweeps, little is known about its functional significance. We used a Massively 
      Parallel Reporter Assay (MPRA) to assay 5,353 high-frequency introgressed 
      variants for their ability to modulate the gene expression within 170 bp of 
      endogenous sequence. We identified 2,548 variants in active putative 
      cis-regulatory elements (CREs) and 292 expression-modulating variants (emVars). 
      These emVars are predicted to alter the binding motifs of important immune 
      transcription factors, are enriched for associations with neutrophil and white 
      blood cell count, and are associated with the expression of genes that function 
      in innate immune pathways including inflammatory response and antiviral defense. 
      We combined the MPRA data with other data sets to identify strong candidates to 
      be driver variants of positive selection including an emVar that may contribute 
      to protection against severe COVID-19 response. We endogenously deleted two CREs 
      containing expression-modulation variants linked to immune function, rs11624425 
      and rs80317430, identifying their primary genic targets as ELMSAN1, and PAN2 and 
      STAT2, respectively, three genes differentially expressed during influenza 
      infection. Overall, we present the first database of experimentally identified 
      expression-modulating Neanderthal-introgressed alleles contributing to potential 
      immune response in modern humans.
CI  - © The Author(s) 2021. Published by Oxford University Press on behalf of the 
      Society for Molecular Biology and Evolution.
FAU - Jagoda, Evelyn
AU  - Jagoda E
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
FAU - Xue, James R
AU  - Xue JR
AD  - Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, 
      MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Reilly, Steven K
AU  - Reilly SK
AD  - Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, 
      MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
FAU - Dannemann, Michael
AU  - Dannemann M
AD  - Department of Evolutionary Genetics, Max Planck Institute for Evolutionary 
      Anthropology, Leipzig, Germany.
AD  - Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu, Estonia.
FAU - Racimo, Fernando
AU  - Racimo F
AD  - Lundbeck GeoGenetics Centre, The Globe Institute, University of Copenhagen, 
      Copenhagen, Denmark.
FAU - Huerta-Sanchez, Emilia
AU  - Huerta-Sanchez E
AD  - Department of Ecology and Evolutionary Biology, Brown University, Providence, RI, 
      USA.
AD  - Center for Computational Molecular Biology, Brown University, Providence, RI, 
      USA.
FAU - Sankararaman, Sriram
AU  - Sankararaman S
AD  - Department of Computer Science, UCLA, Los Angeles, CA, USA.
AD  - Department of Human Genetics, UCLA, Los Angeles, CA, USA.
FAU - Kelso, Janet
AU  - Kelso J
AD  - Department of Evolutionary Genetics, Max Planck Institute for Evolutionary 
      Anthropology, Leipzig, Germany.
FAU - Pagani, Luca
AU  - Pagani L
AD  - Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu, Estonia.
AD  - Department of Biology, University of Padova, Padova, Italy.
FAU - Sabeti, Pardis C
AU  - Sabeti PC
AD  - Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, 
      MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
AD  - Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of 
      Public Health, Boston, MA, USA.
AD  - Howard Hughes Medical Institute, Chevy Chase, MD, USA.
FAU - Capellini, Terence D
AU  - Capellini TD
AD  - Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
AD  - Broad Institute of MIT and Harvard, Cambridge, MA, USA.
LA  - eng
GR  - R35 GM125055/GM/NIGMS NIH HHS/United States
GR  - R35 GM128946/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Mol Biol Evol
JT  - Molecular biology and evolution
JID - 8501455
SB  - IM
MH  - Animals
MH  - Gene Expression
MH  - *Genetic Variation
MH  - *Genome, Human
MH  - Humans
MH  - Immunity, Innate/*genetics
MH  - Inflammation
MH  - *Neanderthals/genetics
PMC - PMC8760939
OTO - NOTNLM
OT  - adaptation
OT  - immune
OT  - introgression
OT  - massively parallel reporter assay
OT  - neandertal
OT  - positive selection
EDAT- 2021/10/19 06:00
MHDA- 2022/01/28 06:00
CRDT- 2021/10/18 17:25
PHST- 2021/10/19 06:00 [pubmed]
PHST- 2022/01/28 06:00 [medline]
PHST- 2021/10/18 17:25 [entrez]
AID - 6400258 [pii]
AID - msab304 [pii]
AID - 10.1093/molbev/msab304 [doi]
PST - ppublish
SO  - Mol Biol Evol. 2022 Jan 7;39(1):msab304. doi: 10.1093/molbev/msab304.

PMID- 34545661
OWN - NLM
STAT- MEDLINE
DCOM- 20220111
LR  - 20230503
IS  - 1740-0929 (Electronic)
IS  - 1344-3941 (Linking)
VI  - 92
IP  - 1
DP  - 2021 Jan-Dec
TI  - Identification of IGF2BP1-related lncRNA-miRNA-mRNA network in goat skeletal 
      muscle satellite cells.
PG  - e13631
LID - 10.1111/asj.13631 [doi]
AB  - Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) plays essential 
      roles in the proliferation of skeletal muscle satellite cells (MuSCs). Increasing 
      evidence has shown that IGF2BP1 regulates the expression of noncoding RNAs and 
      mRNAs. However, the related molecular network remains to be fully understood. 
      Therefore, we performed RNA sequencing and analyzed the microRNAs (miRNAs), long 
      noncoding RNAs (lncRNAs), and mRNAs differentially expressed in goat MuSCs 
      treated with IGF2BP1 overexpressing and empty vectors. A total of 36 miRNAs, 59 
      lncRNAs, and 44 mRNAs were differentially expressed caused by IGF2BP1. 
      Expectedly, they were enriched in muscle development-related Rap1, PI3K-AKT, and 
      FoxO signaling pathways. Finally, we constructed a lncRNA-miRNA-mRNA interaction 
      network containing 30 lncRNAs, 15 miRNAs, and 34 mRNAs, in which several miRNAs, 
      including miR-133a-3p, miR-204-5p, miR-125a-3p, miR-145-3p, and miR-423-5p, 
      relate with cell growth and participate in muscle development. Overall, we 
      constructed an IGF2BP1-related network, which provides new insight into the 
      myogenic proliferation of goat.
CI  - © 2021 Japanese Society of Animal Science.
FAU - Xu, Xiaoli
AU  - Xu X
AUID- ORCID: 0000-0001-6857-7584
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Leng, Junchen
AU  - Leng J
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Zhang, Xiao
AU  - Zhang X
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Capellini, Terence D
AU  - Capellini TD
AD  - Human Evolutionary Biology, Harvard University, Cambridge, Massachusetts, USA.
FAU - Chen, Yuan
AU  - Chen Y
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Yang, Liu
AU  - Yang L
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Chen, Zitong
AU  - Chen Z
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Zheng, Shuailong
AU  - Zheng S
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Zhang, Xujia
AU  - Zhang X
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Zhan, Siyuan
AU  - Zhan S
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Wang, Linjie
AU  - Wang L
AUID- ORCID: 0000-0001-9672-7703
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Zhong, Tao
AU  - Zhong T
AUID- ORCID: 0000-0003-3429-9082
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Guo, Jiazhong
AU  - Guo J
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Niu, Lili
AU  - Niu L
AUID- ORCID: 0000-0003-1510-9466
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Wang, Yan
AU  - Wang Y
AUID- ORCID: 0000-0003-1412-5499
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Dai, Dinghui
AU  - Dai D
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Zhang, Hongping
AU  - Zhang H
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Li, Li
AU  - Li L
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
FAU - Cao, Jiaxue
AU  - Cao J
AD  - Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of 
      Sichuan Province, Sichuan Agricultural University, Chengdu, China.
LA  - eng
GR  - 31802048/National Natural Science Foundation of China/
PT  - Journal Article
PL  - Australia
TA  - Anim Sci J
JT  - Animal science journal = Nihon chikusan Gakkaiho
JID - 100956805
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Gene Regulatory Networks
MH  - Goats/genetics
MH  - *MicroRNAs/genetics
MH  - Phosphatidylinositol 3-Kinases
MH  - *RNA, Long Noncoding
MH  - RNA, Messenger/genetics
MH  - *Satellite Cells, Skeletal Muscle
OTO - NOTNLM
OT  - IGF2BP1
OT  - MuSCs
OT  - ceRNA network
OT  - goat
OT  - lncRNAs
EDAT- 2021/09/22 06:00
MHDA- 2022/01/12 06:00
CRDT- 2021/09/21 06:49
PHST- 2021/07/25 00:00 [revised]
PHST- 2021/02/24 00:00 [received]
PHST- 2021/08/12 00:00 [accepted]
PHST- 2021/09/21 06:49 [entrez]
PHST- 2021/09/22 06:00 [pubmed]
PHST- 2022/01/12 06:00 [medline]
AID - 10.1111/asj.13631 [doi]
PST - ppublish
SO  - Anim Sci J. 2021 Jan-Dec;92(1):e13631. doi: 10.1111/asj.13631.