By the same authors

From the same journal

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

Research output: Contribution to journalArticle

Author(s)

  • 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

Department/unit(s)

Publication details

JournalCell reports
DatePublished - 23 May 2017
Issue number8
Volume19
Number of pages9
Pages (from-to)1503-1511
Original languageEnglish

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.

Bibliographical note

© 2017 The Author(s).

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