Single-Cell Landscape of Transcriptional Heterogeneity and Cell Fate Decisions during Mouse Early Gastrulation

Hisham Mohammed, Irene Hernando-Herraez, Aurora Savino, Antonio Scialdone, Iain Macaulay, Carla Mulas, Tamir Chandra, Thierry Voet, Wendy Dean, Jennifer Nichols, John C. Marioni, Wolf Reik

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

The mouse inner cell mass (ICM) segregates into the epiblast and primitive endoderm (PrE) lineages coincident with implantation of the embryo. The epiblast subsequently undergoes considerable expansion of cell numbers prior to gastrulation. To investigate underlying regulatory principles, we performed systematic single-cell RNA sequencing (seq) of conceptuses from E3.5 to E6.5. The epiblast shows reactivation and subsequent inactivation of the X chromosome, with Zfp57 expression associated with reactivation and inactivation together with other candidate regulators. At E6.5, the transition from epiblast to primitive streak is linked with decreased expression of polycomb subunits, suggesting a key regulatory role. Notably, our analyses suggest elevated transcriptional noise at E3.5 and within the non-committed epiblast at E6.5, coinciding with exit from pluripotency. By contrast, E6.5 primitive streak cells became highly synchronized and exhibit a shortened G1 cell-cycle phase, consistent with accelerated proliferation. Our study systematically charts transcriptional noise and uncovers molecular processes associated with early lineage decisions.

Original languageEnglish (US)
Pages (from-to)1215-1228
Number of pages14
JournalCell Reports
Volume20
Issue number5
DOIs
StatePublished - Aug 1 2017
Externally publishedYes

Keywords

  • X-chromosome
  • embryo
  • epiblast
  • gastrulation
  • primitive endoderm
  • primitive streak
  • single-cell RNA-seq
  • transcriptional noise

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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