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Dev Cell. 2016 Jul 11;38(1):100-15. doi: 10.1016/j.devcel.2016.06.014.

Spatiotemporal Reconstruction of the Human Blastocyst by Single-Cell Gene-Expression Analysis Informs Induction of Naive Pluripotency.

Author information

1
Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA; Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
2
Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA; Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
3
Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA.
4
Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
5
Sage Bionetworks, Seattle, WA 98109, USA.
6
Department of Cell Biology and Neuroscience, Montana State University, Bozeman, MT 59717, USA.
7
Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA; Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: vsebast@stanford.edu.

Abstract

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 in silico precursors of the epiblast and primitive endoderm lineages and revealed a role for MCRS1, TET1, and THAP11 in epiblast formation and their ability to induce naive pluripotency in vitro. Our results highlight the potential of single-cell gene-expression analysis in human preimplantation development to instruct human stem cell biology.

PMID:
27404362
DOI:
10.1016/j.devcel.2016.06.014
[Indexed for MEDLINE]
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