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, Jianping Fu
Author Information
Yi Zheng: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
Xufeng Xue: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
Yue Shao: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
Sicong Wang: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
Sajedeh Nasr Esfahani: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
Zida Li: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.
Jonathon M Muncie: Department of Surgery, Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA, USA.
Johnathon N Lakins: Department of Surgery, Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA, USA.
Valerie M Weaver: Department of Surgery, Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA, USA.
Deborah L Gumucio: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Jianping Fu: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA. jpfu@umich.edu.
Early human embryonic development involves extensive lineage diversification, cell-fate specification and tissue patterning. Despite its basic and clinical importance, early human embryonic development remains relatively unexplained owing to interspecies divergence 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.
References
Cell Stem Cell. 2008 Aug 7;3(2):182-95
[PMID: 18682240]
