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...

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Main Authors:	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
Format:	Online
Language:	English
Published:	Elsevier 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649257/

id	pubmed-4649257
recordtype	oai_dc
spelling	pubmed-46492572015-12-11 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 Article 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. Elsevier 2015-10-17 /pmc/articles/PMC4649257/ /pubmed/26489895 http://dx.doi.org/10.1016/j.stemcr.2015.09.009 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	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
spellingShingle	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 Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells
author_facet	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
author_sort	Ugarte, Fernando
title	Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells
title_short	Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells
title_full	Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells
title_fullStr	Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells
title_full_unstemmed	Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells
title_sort	progressive chromatin condensation and h3k9 methylation regulate the differentiation of embryonic and hematopoietic stem cells
description	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.
publisher	Elsevier
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649257/
_version_	1613502644823785472

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

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