A Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy.

ABSTRACT: To identify the differences between aged and young human hematopoiesis, we performed a direct comparison of aged and young human hematopoietic stem and progenitor cells (HSPCs). Alterations in transcriptome profiles upon aging between humans and mice were then compared. Human specimens consist of CD34+ cells from bone marrow, and mouse specimens of hematopoietic stem cells (HSCs; Lin- Kit+ Sca1+ CD150+). Single-cell transcriptomic studies, functional clustering, and developmental trajectory analyses were performed. A significant increase in multipotent progenitor 2A (MPP2A) cluster is found in the early HSC trajectory in old human subjects. This cluster is enriched in senescence signatures (increased telomere attrition, DNA damage, activation of P53 pathway). In mouse models, the accumulat

SUBMITTER: Poisa-Beiro L 

PROVIDER: S-EPMC11766015 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature