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dc.contributor.authorBeerman, Isabel Eleanor
dc.contributor.authorBock, Christoph
dc.contributor.authorGarrison, Brian Scott
dc.contributor.authorSmith, Zachary D.
dc.contributor.authorGu, Hongcang
dc.contributor.authorMeissner, Alexander
dc.contributor.authorRossi, Derrick J
dc.date.accessioned2014-11-07T16:34:19Z
dc.date.issued2013
dc.identifier.citationBeerman, Isabel, Christoph Bock, Brian S. Garrison, Zachary D. Smith, Hongcang Gu, Alexander Meissner, and Derrick J. Rossi. 2013. “Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging.” Cell Stem Cell 12, no. 4: 413–425.en_US
dc.identifier.issn1934-5909en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13362670
dc.description.abstractThe functional potential of hematopoietic stem cells (HSCs) declines during aging, and in doing so, significantly contributes to hematopoietic pathophysiology in the elderly. To explore the relationship between age-associated HSC decline and the epigenome, we examined global DNA methylation of HSCs during ontogeny in combination with functional analysis. Although the DNA methylome is generally stable during aging, site-specific alterations of DNA methylation occur at genomic regions associated with hematopoietic lineage potential and selectively target genes expressed in downstream progenitor and effector cells. We found that age-associated HSC decline, replicative limits, and DNA methylation are largely dependent on the proliferative history of HSCs, yet appear to be telomere-length independent. Physiological aging and experimentally enforced proliferation of HSCs both led to DNA hypermethylation of genes regulated by Polycomb Repressive Complex 2. Our results provide evidence that epigenomic alterations of the DNA methylation landscape contribute to the functional decline of HSCs during aging.en_US
dc.description.sponsorshipStem Cell and Regenerative Biologyen_US
dc.language.isoen_USen_US
dc.publisherElsevier BVen_US
dc.relation.isversionofdoi:10.1016/j.stem.2013.01.017en_US
dash.licenseMETA_ONLY
dc.titleProliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Agingen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalCell Stem Cellen_US
dash.depositing.authorMeissner, Alexander
dash.embargo.until10000-01-01
dc.identifier.doi10.1016/j.stem.2013.01.017*
workflow.legacycommentscommit DARKen_US
dash.contributor.affiliatedBeerman, Isabel Eleanor
dash.contributor.affiliatedRossi, Derrick
dash.contributor.affiliatedGarrison, Brian Scott
dash.contributor.affiliatedMeissner, Alexander


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