RT Journal Article
SR Electronic
T1 Reconstructing human early embryogenesis in vitro with pluripotent stem cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.12.435175
DO 10.1101/2021.03.12.435175
A1 Berna Sozen
A1 Victoria Jorgensen
A1 Meng Zhu
A1 Tongtong Cui
A1 Magdalena Zernicka-Goetz
YR 2021
UL http://biorxiv.org/content/early/2021/03/12/2021.03.12.435175.abstract
AB Understanding human development is of fundamental biological and clinical importance. Yet despite its significance, insights into early developmental events in humans still remain largely unknown. While recent advances show that stem cells can mimic embryogenesis1–9 to unravel hidden developmental mechanisms, a stem cell-based model of early human embryogenesis is lacking. Here, we use human extended pluripotent stem cells10to reconstitute early human development in 3-dimensions and recapitulate early embryo-like events. We first perform a systematic characterisation to reveal unique signalling requirements for building the human pre-implantation blastocyst. Further, we show that these in vitro stem cell-derived blastocyst-like structures are able to undertake spatiotemporal self-organisation to mimic peri-implantation remodelling in which a polarised rosette opens up the amniotic cavity within a developing disc. The hallmarks of human early development displayed by this stem cell-based in vitro model mimics features of embryonic day 3 to day 9/10 of natural development. Thus, this platform represents a tractable model system to contribute to the basic understanding of cellular and molecular mechanisms governing early embryonic events in humans and to provide valuable insights into the design of differentiation protocols for human stem cells in clinical applications.Competing Interest StatementThe authors have declared no competing interest.