Controlled modelling of human epiblast and amnion development using stem cells

Yi Zheng, Xufeng Xue, Yue Shao, Sicong Wang, Sajedeh Nasr Esfahani, Zida Li, Jonathon M. Muncie, Johnathon N. Lakins, Valerie M. Weaver, Deborah L. Gumucio and Jianping Fu ()
Additional contact information
Yi Zheng: University of Michigan
Xufeng Xue: University of Michigan
Yue Shao: University of Michigan
Sicong Wang: University of Michigan
Sajedeh Nasr Esfahani: University of Michigan
Zida Li: University of Michigan
Jonathon M. Muncie: University of California, San Francisco
Johnathon N. Lakins: University of California, San Francisco
Valerie M. Weaver: University of California, San Francisco
Deborah L. Gumucio: University of Michigan Medical School
Jianping Fu: University of Michigan

Nature, 2019, vol. 573, issue 7774, 421-425

Abstract: Abstract Early human embryonic development involves extensive lineage diversification, cell-fate specification and tissue patterning1. Despite its basic and clinical importance, early human embryonic development remains relatively unexplained owing to interspecies divergence2,3 and limited accessibility to human embryo samples. Here we report that human pluripotent stem cells (hPSCs) in a microfluidic device recapitulate, in a highly controllable and scalable fashion, landmarks of the development of the epiblast and amniotic ectoderm parts of the conceptus, including lumenogenesis of the epiblast and the resultant pro-amniotic cavity, formation of a bipolar embryonic sac, and specification of primordial germ cells and primitive streak cells. We further show that amniotic ectoderm-like cells function as a signalling centre to trigger the onset of gastrulation-like events in hPSCs. Given its controllability and scalability, the microfluidic model provides a powerful experimental system to advance knowledge of human embryology and reproduction. This model could assist in the rational design of differentiation protocols of hPSCs for disease modelling and cell therapy, and in high-throughput drug and toxicity screens to prevent pregnancy failure and birth defects.

Date: 2019
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DOI: 10.1038/s41586-019-1535-2

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