title: Spatiotemporal Reconstruction of the Human Blastocyst by Single-Cell Gene-Expression Analysis Informs Induction of Naive Pluripotency.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA; Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Durruthy-Durruthy
authors.affiliation: 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.
authors.forename: Mark
authors.initials: M
authors.lastname: Wossidlo
authors.affiliation: Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Pai
authors.affiliation: 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.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Gugene
authors.initials: G
authors.lastname: Kang
authors.affiliation: Sage Bionetworks, Seattle, WA 98109, USA.
authors.forename: Larsson
authors.initials: L
authors.lastname: Omberg
authors.affiliation: Department of Obstetrics and Gynecology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Bertha
authors.initials: B
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.affiliation: Department of Cell Biology and Neuroscience, Montana State University, Bozeman, MT 59717, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Reijo Pera
authors.affiliation: 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.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sebastiano
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics*; D047108:Embryonic Development; D004707:Endoderm / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D050437:Genes, Developmental; D005855:Germ Layers / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D059010:Single-Cell Analysis / Q000379:methods*
chemical_list: D015415:Biomarkers; C113292:MCRS1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C498470:THAP11 protein, human; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human