An age-progressive platelet differentiation path from hematopoietic stem cells causes exacerbated thrombosis.

ABSTRACT: Platelet dysregulation is drastically increased with advanced age and contributes to making cardiovascular disorders the leading cause of death of elderly humans. Here, we reveal a direct differentiation pathway from hematopoietic stem cells into platelets that is progressively propagated upon aging. Remarkably, the aging-enriched platelet path is decoupled from all other hematopoietic lineages, including erythropoiesis, and operates as an additional layer in parallel with canonical platelet production. This results in two molecularly and functionally distinct populations of megakaryocyte progenitors. The age-induced megakaryocyte progenitors have a profoundly enhanced capacity to engraft, expand, restore, and reconstitute platelets in situ and upon transplantation and produce an additiona

SUBMITTER: Poscablo DM 

PROVIDER: S-EPMC12047039 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature