Spatiotemporal Reconstruction of the Human Blastocyst by Single-Cell Gene-Expression Analysis Informs Induction of Naive Pluripotency
Jens Durruthy-Durruthy, Mark Wossidlo, Sunil Pai, Yusuke Takahashi, Gugene Kang, Larsson Omberg, Bertha Chen, Hiromitsu Nakauchi, Renee Reijo Pera, Vittorio Sebastiano
Human preimplantation embryo development involves complex cellular and molecular events that lead to the establishment of three cell lineages in the blastocyst: trophectoderm, primitive endoderm, and epiblast. Owing to limited resources of biological specimens, our understanding of how the earliest lineage commitments are regulated remains narrow. Here, we examined gene expression in 241 individual cells from early and late human blastocysts to delineate dynamic gene-expression changes. We distinguished all three lineages and further developed a 3D model of the inner cell mass and trophectoderm in which individual cells were mapped into distinct expression domains. We identified inÂ silico precursors of the epiblast and primitive endoderm lineages and revealed a role for MCRS1, TET1, and THAP11 inÂ epiblast formation and their ability to induce naiveÂ pluripotency inÂ vitro. Our results highlight the potential of single-cell gene-expression analysis in human preimplantation development to instruct human stem cell biology. Human early embryogenesis is poorly understood. Durruthy-Durruthy, Wossidlo, etÂ al. perform single-cell gene-expression analysis of early and late human blastocysts and develop a 3D blastocyst model that maps cells to expression domains. They also identify epiblast and primitive endoderm lineage precursors and factors that induce naive pluripotency inÂ vitro.
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