NDLI: The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion

Content Provider	PubMed Central
Author	Kamminga, Leonie M. Bystrykh, Leonid V. Boer, Aletta De Houwer, Sita Douma, José Weersing, Ellen Bert, Dontje Haan, Gerald De
Copyright Year	2006
Abstract	The molecular mechanism responsible for a decline of stem cell functioning after replicative stress remains unknown. We used mouse embryonic fibroblasts (MEFs) and hematopoietic stem cells (HSCs) to identify genes involved in the process of cellular aging. In proliferating and senescent MEFs one of the most differentially expressed transcripts was Enhancer of zeste homolog 2 (Ezh2), a Polycomb group protein (PcG) involved in histone methylation and deacetylation. Retroviral overexpression of Ezh2 in MEFs resulted in bypassing of the senescence program. More importantly, whereas normal HSCs were rapidly exhausted after serial transplantations, overexpression of Ezh2 completely conserved long-term repopulating potential. Animals that were reconstituted with 3 times serially transplanted control bone marrow cells all died due to hematopoietic failure. In contrast, similarly transplanted Ezh2-overexpressing stem cells restored stem cell quality to normal levels. In a “genetic genomics” screen, we identified novel putative Ezh2 target or partner stem cell genes that are associated with chromatin modification. Our data suggest that stabilization of the chromatin structure preserves HSC potential after replicative stress.
Related Links	http://dx.doi.org/10.1182/blood-2005-09-3585
Ending Page	2179
Page Count	10
Starting Page	2170
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	5
Volume Number	107
Language	English
Publisher	© 2006 by The American Society of Hematology
Publisher Date	2006-03-01
Access Restriction	Open
Rights Holder	© 2006 by The American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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STEM CELLS IN HEMATOLOGY (2005)

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