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

Ugarte, Fernando; Sousae, Rebekah; Cinquin, Bertrand; Martin, Eric W.; Krietsch, Jana; Sanchez, Gabriela; Inman, Margaux; Tsang, Herman; Warr, Matthew; Passegué, Emmanuelle; Larabell, Carolyn A.; Forsberg, E. Camilla

doi:10.1016/j.stemcr.2015.09.009

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

Journal Article · Sun Nov 01 00:00:00 EDT 2015 · Stem Cell Reports

DOI:https://doi.org/10.1016/j.stemcr.2015.09.009· OSTI ID:1242997

Ugarte, Fernando; Sousae, Rebekah; Cinquin, Bertrand; Martin, Eric W.; Krietsch, Jana; Sanchez, Gabriela; Inman, Margaux; Tsang, Herman; Warr, Matthew; Passegué, Emmanuelle; Larabell, Carolyn A.; Forsberg, E. Camilla

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

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

OSTI ID:: 1242997

Alternate ID(s):: OSTI ID: 1257345

Journal Information:: Stem Cell Reports, Journal Name: Stem Cell Reports Vol. 5 Journal Issue: 5; ISSN 2213-6711

Publisher:: ElsevierCopyright Statement

Country of Publication:: Netherlands

Language:: English

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Cited by: 76 works

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