期刊
NATURE
卷 573, 期 7774, 页码 421-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-019-1535-2
关键词
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资金
- University of Michigan Mechanical Engineering Faculty Support Fund
- University of Michigan Mcubed Fund
- National Institutes of Health [R01 DK089933]
- California Institute for Regenerative Medicine [RB5-07409]
- University of Michigan
- Lurie Nanofabrication Facility at the University of Michigan
- Michigan-Cambridge Research Initiative
Early human embryonic development involves extensive lineage diversification, cell-fate specification and tissue patterning(1). Despite its basic and clinical importance, early human embryonic development remains relatively unexplained owing to interspecies divergence(2,3) 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.
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