Amnion signals are essential for mesoderm formation in primates.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
26 08 2021
Historique:
received: 12 11 2020
accepted: 22 07 2021
entrez: 27 8 2021
pubmed: 28 8 2021
medline: 23 9 2021
Statut: epublish

Résumé

Embryonic development is largely conserved among mammals. However, certain genes show divergent functions. By generating a transcriptional atlas containing >30,000 cells from post-implantation non-human primate embryos, we uncover that ISL1, a gene with a well-established role in cardiogenesis, controls a gene regulatory network in primate amnion. CRISPR/Cas9-targeting of ISL1 results in non-human primate embryos which do not yield viable offspring, demonstrating that ISL1 is critically required in primate embryogenesis. On a cellular level, mutant ISL1 embryos display a failure in mesoderm formation due to reduced BMP4 signaling from the amnion. Via loss of function and rescue studies in human embryonic stem cells we confirm a similar role of ISL1 in human in vitro derived amnion. This study highlights the importance of the amnion as a signaling center during primate mesoderm formation and demonstrates the potential of in vitro primate model systems to dissect the genetics of early human embryonic development.

Identifiants

pubmed: 34446705
doi: 10.1038/s41467-021-25186-2
pii: 10.1038/s41467-021-25186-2
pmc: PMC8390679
doi:

Substances chimiques

Bone Morphogenetic Protein 4 0
LIM-Homeodomain Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

5126

Subventions

Organisme : NICHD NIH HHS
ID : R21 HD100931
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS113518
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States

Informations de copyright

© 2021. The Author(s).

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Auteurs

Ran Yang (R)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Alexander Goedel (A)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Yu Kang (Y)

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.

Chenyang Si (C)

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.

Chu Chu (C)

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.

Yi Zheng (Y)

Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.

Zhenzhen Chen (Z)

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.

Peter J Gruber (PJ)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Department of Surgery, Yale University, New Haven, CT, USA.

Yao Xiao (Y)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Chikai Zhou (C)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Nevin Witman (N)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Elif Eroglu (E)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Chuen-Yan Leung (CY)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

Yongchang Chen (Y)

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.

Jianping Fu (J)

Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.

Weizhi Ji (W)

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China. wji@lpbr.cn.

Fredrik Lanner (F)

Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. fredrik.lanner@ki.se.
Division of Obstetrics and Gynecology, Karolinska Universitetssjukhuset, Stockholm, Sweden. fredrik.lanner@ki.se.
Ming Wai Lau Center for Reparative Medicine, Stockholm Node, Karolinska Institutet, Stockholm, Sweden. fredrik.lanner@ki.se.

Yuyu Niu (Y)

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China. niuyy@lpbr.cn.
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China. niuyy@lpbr.cn.

Kenneth R Chien (KR)

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. kenneth.chien@ki.se.

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