TY - JOUR T1 - Essential amnion signals for primate primitive streak formation resolved by scRNA map JF - bioRxiv DO - 10.1101/2020.05.28.118703 SP - 2020.05.28.118703 AU - Ran Yang AU - Alexander Goedel AU - Yu Kang AU - Chenyang Si AU - Chu Chu AU - Yi Zheng AU - Zhenzhen Chen AU - Peter J. Gruber AU - Yao Xiao AU - Chikai Zhou AU - Chuen-Yan Leung AU - Yongchang Chen AU - Jianping Fu AU - Weizhi Ji AU - Fredrik Lanner AU - Yuyu Niu AU - Kenneth Chien Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/28/2020.05.28.118703.abstract N2 - The signaling network governing the formation of the primitive streak is well understood in mice, but largely unexplored in primates. Advances in single-cell technology and in vitro embryo culture have enabled to characterize the major cell populations involved. However, a detailed map of this process and insights into its regulatory networks are lacking. Herein, we generated a serial single cell atlas of over 30,000 cells spanning peri-implantation to early primitive streak stages in non-human primates (NHP) describing the emergence of the primitive streak, extraembryonic mesenchyme and amnion. We discovered that ISL1, a gene with a well-established role in cardiogenesis, controls a gene regulatory network in primate amniotic cells. Strikingly, CRISPR/Cas9-targeting of ISL1 resulted in NHP embryos failing to form primitive streak. BMP4 was identified as a key signaling pathway in this process. This was confirmed in human embryonic stem cell lines, suggesting a conserved function in humans. Notably, no viable ISL1 hypomorphic NHP mutant embryos could be recovered after embryo transfer confirming the essential requirement of ISL1. This highlights the importance of the amnion as a signaling center during primate embryogenesis and demonstrates the potential of in vitro primate model systems to investigate the genetics of early human development.Competing Interest StatementThe authors have declared no competing interest. ER -