Abstract
SummaryHuman naive pluripotent cells can differentiate into extraembryonic trophectoderm and hypoblast. Here we describe a human embryo model (blastoid) generated by self-organization. Brief induction of trophectoderm leads to formation of blastocyst-like structures within 3 days. Blastoids are composed of three tissue layers displaying exclusive lineage markers, mimicking the natural blastocyst. Single-cell transcriptome analyses confirm segregation of trophectoderm, hypoblast, and epiblast with high fidelity to the human embryo. This versatile and scalable system provides a robust experimental model for human embryo research.
Highlights
Natural development of the human embryo is challenging to study in vivo and few embryos are available for research in vitro
We found that human naive pluripotent stem cells can generate mixed cultures comprising the three founding lineages of the blastocyst (Guo et al, 2021)
Trophectoderm differentiation is initiated by inhibition of ERK and NODAL signaling using small molecules PD0325901 and A83-01 (PD+A83)
Summary
Natural development of the human embryo is challenging to study in vivo and few embryos are available for research in vitro. Scientists have relied heavily on observations and experiments in other mammals, in particular mice. Embryology unfolds according to a similar overall program in all mammals, there are many distinctions between species. The blastocyst is a landmark of eutherian development that is essential for uterine implantation. Blastocyst formation initiates with delamination of epithelial trophectoderm cells on the surface of the unspecified morula. The trophectoderm forms a fluid-filled cavity and the internal inner cell mass (ICM) cells differentiate into two further lineages, epiblast and hypoblast ( known as primitive endoderm). The mature blastocyst formed by embryonic day 6 (E6) in human is a simple cavitated structure comprising three topologically and molecularly segregated lineages, each of which is critical for further development
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