Proliferation-dependent alterations of the DNA methylation landscape underlie hematopoietic stem cell aging.

ABSTRACT: The 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 indep

SUBMITTER: Beerman I 

PROVIDER: S-EPMC12163706 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature