Self-patterning of human stem cells into post-implantation lineages

Monique Pedroza, Seher Ipek Gassaloglu, Nicolas Dias, Liangwen Zhong, Tien-Chi Jason Hou, Helene Kretzmer, Zachary D. Smith and Berna Sozen ()
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Monique Pedroza: Yale University
Seher Ipek Gassaloglu: Yale University
Nicolas Dias: Yale University
Liangwen Zhong: Yale University
Tien-Chi Jason Hou: Yale University
Helene Kretzmer: Max Planck Institute for Molecular Genetics
Zachary D. Smith: Yale University
Berna Sozen: Yale University

Nature, 2023, vol. 622, issue 7983, 574-583

Abstract: Abstract Investigating human development is a substantial scientific challenge due to the technical and ethical limitations of working with embryonic samples. In the face of these difficulties, stem cells have provided an alternative to experimentally model inaccessible stages of human development in vitro1–13. Here we show that human pluripotent stem cells can be triggered to self-organize into three-dimensional structures that recapitulate some key spatiotemporal events of early human post-implantation embryonic development. Our system reproducibly captures spontaneous differentiation and co-development of embryonic epiblast-like and extra-embryonic hypoblast-like lineages, establishes key signalling hubs with secreted modulators and undergoes symmetry breaking-like events. Single-cell transcriptomics confirms differentiation into diverse cell states of the perigastrulating human embryo14,15 without establishing placental cell types, including signatures of post-implantation epiblast, amniotic ectoderm, primitive streak, mesoderm, early extra-embryonic endoderm, as well as initial yolk sac induction. Collectively, our system captures key features of human embryonic development spanning from Carnegie stage16 4–7, offering a reproducible, tractable and scalable experimental platform to understand the basic cellular and molecular mechanisms that underlie human development, including new opportunities to dissect congenital pathologies with high throughput.

Date: 2023
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DOI: 10.1038/s41586-023-06354-4

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