4.7 Article

Cell Fate Potential of Human Pluripotent Stem Cells Is Encoded by Histone Modifications

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CELL STEM CELL
卷 9, 期 1, 页码 24-36

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CELL PRESS
DOI: 10.1016/j.stem.2011.06.002

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  1. Canadian Institute of Health Research
  2. Ontario Ministry of Research Innovation-(OCRiT GL2)
  3. Canadian Chair Program

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Human embryonic stem cells (hESCs) expressing pluripotency markers are assumed to possess equipotent developmental potential. However, disparate responses to differentiation stimuli functionally illustrate that hESCs generate a spectrum of differentiated cell types, suggestive of lineage bias. Here, we reveal specific cell surface markers that allow sub-fractionation of hESCs expressing hallmark markers of pluripotency. By direct de novo isolation of these subsets, we demonstrate that propensities for lineage differentiation are balanced with reduced clonogenic self-renewal. Histone modification marks of gene loci associated with pluripotency versus lineage specificity predicted cell fate potential of these subfractions, thereby supporting the absence of uniform bivalency as a molecular paradigm to describe cell fate determination of pluripotent cells. Our study reveals that cell fate potential is encoded within cells comprising hESC cultures, highlighting them as a means to understand the mechanisms of lineage specification of pluripotent cells.

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