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

Cell Rep. 2017 May 23;19(8):1503-1511. doi: 10.1016/j.celrep.2017.04.074.


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.

Keywords: JAK2; aging; cancer; cellular aging; genomics; hematology; leukemia; p53; scRNA-seq; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Compartmentation*
  • Cell Cycle
  • Cell Proliferation
  • Cellular Senescence*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Janus Kinase 2
  • Mice
  • Myeloid Cells / metabolism
  • Transcription Factors / metabolism


  • Transcription Factors
  • JAK2 protein, human
  • Janus Kinase 2