Single-cell gene expression profiles define self-renewing, pluripotent, and lineage primed states of human pluripotent stem cells

Shelley R. Hough, Matthew Thornton, Elizabeth Mason, Jessica C. Mar, Christine A. Wells, Martin F. Pera

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Pluripotent stem cells display significant heterogeneity in gene expression, but whether this diversity is an inherent feature of the pluripotent state remains unknown. Single-cell gene expression analysis in cell subsets defined by surface antigen expression revealed that human embryonic stem cell cultures exist as a continuum of cell states, even under defined conditions that drive self-renewal. The majority of the population expressed canonical pluripotency transcription factors and could differentiate into derivatives of all three germ layers. A minority subpopulation of cells displayed high self-renewal capacity, consistently high transcripts for all pluripotency-related genes studied, and no lineage priming. This subpopulation was characterized by its expression of a particular set of intercellular signaling molecules whose genes shared common regulatory features. Our data support a model of an inherently metastable self-renewing population that gives rise to a continuum of intermediate pluripotent states, which ultimately become primed for lineage specification.

Original languageEnglish (US)
Pages (from-to)881-895
Number of pages15
JournalStem Cell Reports
Volume2
Issue number6
DOIs
StatePublished - Jun 3 2014

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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