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bioRxiv · 10.1101/2020.05.28.118703

Essential amnion signals for primate primitive streak formation resolved by scRNA map

Yang, R.·Goedel, A.·Kang, Y.·Si, C.·Chu, C.·Zheng, Y.·Chen, Z.·Gruber, P. J.·Xiao, Y.·Zhou, C.·Leung, C.-Y.·Chen, Y.·Fu, J.·Ji, W.·Lanner, F.·Niu, Y.·Chien, K. R.
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Abstract

Essential genes for murine embryonic development can demonstrate a disparate phenotype in human cohorts. By generating a transcriptional atlas containing >30,000 cells from postimplantation non-human primate embryos, we discovered that ISL1, a gene with a well-established role in cardiogenesis, controls a gene regulatory network in primate amnion. CRISPR/Cas9-targeting of ISL1 resulted in non-human primate embryos which did not yield viable offspring, demonstrating that ISL1 is critically required in primate embryogenesis. On a cellular level, mutant ISL1 embryos displayed 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 confirmed 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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Yang, R., Goedel, A., Kang, Y., Si, C., Chu, C., Zheng, Y., Chen, Z., Gruber, P. J., Xiao, Y., Zhou, C., Leung, C.-Y., Chen, Y., Fu, J., Ji, W., Lanner, F., Niu, Y., Chien, K. R.. 2020-05-28. Essential amnion signals for primate primitive streak formation resolved by scRNA map. https://doi.org/10.1101/2020.05.28.118703

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