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Integrated analysis of single-cell embryo data yields a unified transcriptome signature for the human pre-implantation epiblast.

Authors
  • Stirparo, Giuliano G1
  • Boroviak, Thorsten1
  • Guo, Ge1
  • Nichols, Jennifer1, 2
  • Smith, Austin1, 3
  • Bertone, Paul4
  • 1 Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
  • 2 Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 3EG, UK.
  • 3 Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK.
  • 4 Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK [email protected]
Type
Published Article
Journal
Development
Publisher
The Company of Biologists
Publication Date
Feb 07, 2018
Volume
145
Issue
3
Identifiers
DOI: 10.1242/dev.158501
PMID: 29361568
Source
Medline
Keywords
License
Unknown

Abstract

Single-cell profiling techniques create opportunities to delineate cell fate progression in mammalian development. Recent studies have provided transcriptome data from human pre-implantation embryos, in total comprising nearly 2000 individual cells. Interpretation of these data is confounded by biological factors, such as variable embryo staging and cell-type ambiguity, as well as technical challenges in the collective analysis of datasets produced with different sample preparation and sequencing protocols. Here, we address these issues to assemble a complete gene expression time course spanning human pre-implantation embryogenesis. We identify key transcriptional features over developmental time and elucidate lineage-specific regulatory networks. We resolve post-hoc cell-type assignment in the blastocyst, and define robust transcriptional prototypes that capture epiblast and primitive endoderm lineages. Examination of human pluripotent stem cell transcriptomes in this framework identifies culture conditions that sustain a naïve state pertaining to the inner cell mass. Our approach thus clarifies understanding both of lineage segregation in the early human embryo and of in vitro stem cell identity, and provides an analytical resource for comparative molecular embryology.

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