Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging
Beerman et al, Cell Stem Cell 2013 copy.pdf (2.035Mb)
Access StatusFull text of the requested work is not available in DASH at this time ("restricted access"). For more information on restricted deposits, see our FAQ.
Smith, Zachary D.
MetadataShow full item record
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.
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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13362670
- FAS Scholarly Articles 
Contact administrator regarding this item (to report mistakes or request changes)