Megakaryocyte progenitor cell function is enhanced upon aging despite the functional decline of aged hematopoietic stem cells.
Stem Cell Reports
; 16(6): 1598-1613, 2021 06 08.
Article
en En
| MEDLINE
| ID: mdl-34019813
ABSTRACT
Age-related morbidity is associated with a decline in hematopoietic stem cell (HSC) function, but the mechanisms of HSC aging remain unclear. We performed heterochronic HSC transplants followed by quantitative analysis of cell reconstitution. Although young HSCs outperformed old HSCs in young recipients, young HSCs unexpectedly failed to outcompete the old HSCs of aged recipients. Interestingly, despite substantial enrichment of megakaryocyte progenitors (MkPs) in old mice in situ and reported platelet (Plt) priming with age, transplanted old HSCs were deficient in reconstitution of all lineages, including MkPs and Plts. We therefore performed functional analysis of young and old MkPs. Surprisingly, old MkPs displayed unmistakably greater regenerative capacity compared with young MkPs. Transcriptome analysis revealed putative molecular regulators of old MkP expansion. Collectively, these data demonstrated that aging affects HSCs and megakaryopoiesis in fundamentally different ways whereas old HSCs functionally decline, MkPs gain expansion capacity upon aging.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Envejecimiento
/
Células Madre Hematopoyéticas
/
Trombopoyesis
/
Células Progenitoras de Megacariocitos
/
Transcriptoma
Límite:
Animals
Idioma:
En
Revista:
Stem Cell Reports
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos