Megakaryocyte progenitor cell function is enhanced upon aging despite the functional decline of aged hematopoietic stem cells

• DOI: 10.1016/j.stemcr.2021.04.016
• Publication Date: 2021-05-20T14:48:53Z
• Authors: Donna M. Poscablo; Atesh K. Worthington; Stephanie Smith-B...; E. Camilla Forsberg
• Keywords: Progenitor; Hematopoietic stem cell

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 transplants followed by quantitative analysis reconstitution. Although young HSCs outperformed old recipients, unexpectedly failed to outcompete aged recipients. Interestingly, despite substantial enrichment megakaryocyte progenitors (MkPs) mice situ and reported platelet (Plt) priming age, transplanted were deficient reconstitution all lineages, including MkPs Plts. therefore functional MkPs. Surprisingly, displayed unmistakably greater regenerative capacity compared Transcriptome revealed putative molecular regulators MkP expansion. Collectively, these data demonstrated that affects megakaryopoiesis fundamentally different ways: whereas functionally decline, gain expansion upon aging.