Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment.

K Kirschner, T Chandra, V Kiselev, D Flores-Santa Cruz, IC Macaulay, HJ Park, J Li, DG Kent, R Kumar, DC Pask, TL Hamilton, M Hemberg, W Reik, AR Green

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)1503-1511
Number of pages9
JournalCell reports
Issue number8
Publication statusPublished - 23 May 2017

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© 2017 The Author(s).

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