Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment
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Peer-reviewed
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Abstract
Aging of the hematopoietic stem cell (HSC) compartment is characterized by lineage bias and reduced stem cell function, the molecular basis of which is largely unknown. Using single-cell transcriptomics, we identified a distinct subpopulation of old HSCs carrying a p53 signature indicative of stem cell decline alongside pro-proliferative JAK/STAT signaling. To investigate the relationship between JAK/STAT and p53 signaling, we challenged HSCs with a constitutively active form of JAK2 (V617F) and observed an expansion of the p53-positive subpopulation in old mice. Our results reveal cellular heterogeneity in the onset of HSC aging and implicate a role for JAK2V617F-driven proliferation in the p53-mediated functional decline of old HSCs.
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Keywords
JAK2, aging, cancer, cellular aging, genomics, hematology, leukemia, p53, scRNA-seq, stem cells, Animals, Cell Compartmentation, Cell Cycle, Cell Proliferation, Cellular Senescence, Hematopoietic Stem Cells, Janus Kinase 2, Mice, Myeloid Cells, Transcription Factors
Journal Title
Cell Reports
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2211-1247
2211-1247
2211-1247
Volume Title
19
Publisher
Elsevier
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Sponsorship
Medical Research Council (MC_PC_12009)
Wellcome Trust (104710/Z/14/Z)
Leukaemia & Lymphoma Research (13003)
Blood Cancer UK (07037)
Cancer Research UK (21762)
Wellcome Trust (104710/Z/14/Z)
Leukaemia & Lymphoma Research (13003)
Blood Cancer UK (07037)
Cancer Research UK (21762)