Journal
STEM CELL REPORTS
Volume 2, Issue 6, Pages 881-895Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2014.04.014
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Funding
- California Institute of Regenerative Medicine (Basic Biology) [RB1-01372, RL1-00667-1]
- Human Science Frontiers Program [RGP0001/2012]
- Australian Research Council
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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.
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