An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state
2013 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 121, no 21, 4257-4264 p.Article in journal (Refereed) Published
Aging of hematopoietic stem cells (HSCs) leads to several functional changes, including alterations affecting self-renewal and differentiation. Although it is well established that many of the age-induced changes are intrinsic to HSCs, less is known regarding the stability of this state. Here, we entertained the hypothesis that HSC aging is driven by the acquisition of permanent genetic mutations. To examine this issue at a functional level in vivo, we applied induced pluripotent stem (iPS) cell reprogramming of aged hematopoietic progenitors and allowed the resulting aged-derived iPS cells to reform hematopoiesis via blastocyst complementation. Next, we functionally characterized iPS-derived HSCs in primary chimeras and after the transplantation of re-differentiated HSCs into new hosts, the gold standard to assess HSC function. Our data demonstrate remarkably similar functional properties of iPS-derived and endogenous blastocyst-derived HSCs, despite the extensive chronological and proliferative age of the former. Our results, therefore, favor a model in which an underlying, but reversible, epigenetic component is a hallmark of HSC aging.
Place, publisher, year, edition, pages
American Society of Hematology , 2013. Vol. 121, no 21, 4257-4264 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-96433DOI: 10.1182/blood-2012-11-469080ISI: 000321873900007OAI: oai:DiVA.org:liu-96433DiVA: diva2:641816
Funding Agencies|Swedish Cancer Society||Swedish Medical Research Council||Swedish Pediatric Leukemia Foundation, Ingabritt och Arne Lundbergs Forskningsstiftelse||AFA Insurance||2013-08-192013-08-192013-08-19