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 journalArticle

47 Citations (Scopus)

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

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Pluripotent Stem Cells
Stem cells
Transcriptome
Gene expression
Genes
Surface Antigens
Cell culture
Transcription Factors
Cells
Derivatives
Specifications
Gene Expression
Germ Layers
Molecules
Population
Cell Culture Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Developmental Biology
  • Genetics
  • Medicine(all)

Cite this

Single-cell gene expression profiles define self-renewing, pluripotent, and lineage primed states of human pluripotent stem cells. / Hough, Shelley R.; Thornton, Matthew; Mason, Elizabeth; Mar, Jessica C.; Wells, Christine A.; Pera, Martin F.

In: Stem Cell Reports, Vol. 2, No. 6, 03.06.2014, p. 881-895.

Research output: Contribution to journalArticle

Hough, Shelley R. ; Thornton, Matthew ; Mason, Elizabeth ; Mar, Jessica C. ; Wells, Christine A. ; Pera, Martin F. / Single-cell gene expression profiles define self-renewing, pluripotent, and lineage primed states of human pluripotent stem cells. In: Stem Cell Reports. 2014 ; Vol. 2, No. 6. pp. 881-895.
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