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Yang R, Goedel A, Kang Y, Si C, Chu C, Zheng Y, Chen Z, Gruber PJ, Xiao Y, Zhou C, Witman N, Eroglu E, Leung CY, Chen Y, Fu J, Ji W, Lanner F, Niu Y, Chien KR
Nat Commun 12 (1) 5126 [2021-08-26; online 2021-08-26]
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.
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PubMed 34446705
DOI 10.1038/s41467-021-25186-2
Crossref 10.1038/s41467-021-25186-2
pmc: PMC8390679
pii: 10.1038/s41467-021-25186-2