Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment
Flores-Santa Cruz, D
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Kirschner, K., Chandra, T., Kiselev, V., Flores-Santa Cruz, D., Macaulay, I., Park, H., Li, J., et al. (2017). Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment. Cell Reports, 19 (8), 1503-1511. https://doi.org/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.
WELLCOME TRUST (104710/Z/14/Z)
External DOI: https://doi.org/10.1016/j.celrep.2017.04.074
This record's URL: https://www.repository.cam.ac.uk/handle/1810/265732