Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells
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. Lastly, our results demonstrate global chromatin rearrangements during stem cell differentiation and that heterochromatin formation by H3K9 methylation regulates HSC differentiation.
- Authors:
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1242997
- Alternate Identifier(s):
- OSTI ID: 1257345
- 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
- Resource Type:
- Published Article
- Journal Name:
- Stem Cell Reports
- Additional Journal Information:
- Journal Name: Stem Cell Reports Journal Volume: 5 Journal Issue: 5; Journal ID: ISSN 2213-6711
- Publisher:
- Elsevier
- Country of Publication:
- Netherlands
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES
Citation Formats
Ugarte, Fernando, Sousae, Rebekah, Cinquin, Bertrand, Martin, Eric W., Krietsch, Jana, Sanchez, Gabriela, Inman, Margaux, Tsang, Herman, Warr, Matthew, Passegué, Emmanuelle, Larabell, Carolyn A., and Forsberg, E. Camilla. Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells. Netherlands: N. p., 2015.
Web. doi:10.1016/j.stemcr.2015.09.009.
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. Netherlands. https://doi.org/10.1016/j.stemcr.2015.09.009
Ugarte, Fernando, Sousae, Rebekah, Cinquin, Bertrand, Martin, Eric W., Krietsch, Jana, Sanchez, Gabriela, Inman, Margaux, Tsang, Herman, Warr, Matthew, Passegué, Emmanuelle, Larabell, Carolyn A., and Forsberg, E. Camilla. Sun .
"Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells". Netherlands. https://doi.org/10.1016/j.stemcr.2015.09.009.
@article{osti_1242997,
title = {Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells},
author = {Ugarte, Fernando and Sousae, Rebekah and Cinquin, Bertrand and Martin, Eric W. and Krietsch, Jana and Sanchez, Gabriela and Inman, Margaux and Tsang, Herman and Warr, Matthew and Passegué, Emmanuelle and Larabell, Carolyn A. and Forsberg, E. Camilla},
abstractNote = {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.},
doi = {10.1016/j.stemcr.2015.09.009},
journal = {Stem Cell Reports},
number = 5,
volume = 5,
place = {Netherlands},
year = {Sun Nov 01 00:00:00 EDT 2015},
month = {Sun Nov 01 00:00:00 EDT 2015}
}
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https://doi.org/10.1016/j.stemcr.2015.09.009
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