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Aging is invariably associated with alterations of the hematopoietic stem cell (HSC) compartment, including loss of functional capacity, altered clonal composition, and changes in lineage contribution. Although accumulation of DNA damage occurs during HSC aging, it is unlikely such consistent aging phenotypes could be solely attributed to changes in DNA integrity. Another mechanism by which heritable traits could contribute to the changes in the functional potential of aged HSCs is through alterations in the epigenetic landscape of adult stem cells. Indeed, recent studies on hematopoietic stem cells have suggested that altered epigenetic profiles are associated with HSC aging and play a key role in modulating the functional potential of HSCs at different stages during ontogeny. Even small changes of the epigenetic landscape can lead to robustly altered expression patterns, either directly by loss of regulatory control or through indirect, additive effects, ultimately leading to transcriptional changes of the stem cells. Potential drivers of such changes in the epigenetic landscape of aged HSCs include proliferative history, DNA damage, and deregulation of key epigenetic enzymes and complexes. This review will focus largely on the two most characterized epigenetic marks - DNA methylation and histone modifications - but will also discuss the potential role of non-coding RNAs in regulating HSC function during aging.
Pubmed ID: 25261778 RIS Download
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SEER collects cancer incidence data from population-based cancer registries covering approximately 47.9 percent of the U.S. population. The SEER registries collect data on patient demographics, primary tumor site, tumor morphology, stage at diagnosis, and first course of treatment, and they follow up with patients for vital status.There are two data products available: SEER Research and SEER Research Plus. This was motivated because of concerns about the increasing risk of re-identifiability of individuals. The Research Plus databases require more rigorous process for access that includes user authentication through Institutional Account or multiple-step request process for Non-Institutional users.
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