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

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. Lastly, our results demonstrate global chromatin rearrangements during stem cell differentiation and that heterochromatin formation by H3K9 methylation regulates HSC differentiation.
Authors:
 [1] ;  [1] ;  [2] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [3] ;  [3] ;  [2] ;  [1]
  1. Univ. of California, Santa Cruz, CA (United States)
  2. Univ. of California, San Francisco, CA (United States). National Center for X-ray Tomography; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  3. Univ. of California, San Francisco, CA (United States). The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research
Publication Date:
Grant/Contract Number:
AC02-05CH11231; R01HL115158; 3497; P41GM103445; TG2-01157; R25GM058903; TB1-01195; CL1-00506; FA1-00617-1; RN1-00540; RSG-13-193-01-DDC
Type:
Published Article
Journal Name:
Stem Cell Reports
Additional Journal Information:
Journal Volume: 5; Journal Issue: 5; Journal ID: ISSN 2213-6711
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES
OSTI Identifier:
1242997
Alternate Identifier(s):
OSTI ID: 1257345