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Stem Cell Reports. 2015 Nov 10;5(5):728-740. doi: 10.1016/j.stemcr.2015.09.009. Epub 2015 Oct 17.

Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells.

Author information

1
Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
2
National Center for X-ray Tomography, UCSF, San Francisco, CA 94143, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
3
The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Medicine Department, Hem/Onc Division, University of California, San Francisco, San Francisco, CA 94143, USA.
4
Institute for the Biology of Stem Cells, Department of Biomolecular Engineering, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. Electronic address: cforsber@soe.ucsc.edu.

Abstract

Epigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization affects the lineage potential of stem cells and that manipulation of chromatin dynamics influences stem cell function. Using nuclease sensitivity assays, we found a progressive decrease in chromatin digestion among pluripotent embryonic stem cells (ESCs), multipotent hematopoietic stem cells (HSCs), and mature hematopoietic cells. Quantitative high-resolution microscopy revealed that ESCs contain significantly more euchromatin than HSCs, with a further reduction in mature cells. Increased cellular maturation also led to heterochromatin localization to the nuclear periphery. Functionally, prevention of heterochromatin formation by inhibition of the histone methyltransferase G9A resulted in delayed HSC differentiation. Our results demonstrate global chromatin rearrangements during stem cell differentiation and that heterochromatin formation by H3K9 methylation regulates HSC differentiation.

PMID:
26489895
PMCID:
PMC4649257
DOI:
10.1016/j.stemcr.2015.09.009
[Indexed for MEDLINE]
Free PMC Article

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