Kirschner, K, Chandra, T, Kiselev, V et al. (11 more authors) (2017) Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment. Cell reports. pp. 1503-1511. ISSN 2211-1247
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 The Author(s). |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 02 Oct 2019 09:20 |
Last Modified: | 16 Oct 2024 16:05 |
Published Version: | https://doi.org/10.1016/j.celrep.2017.04.074 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1016/j.celrep.2017.04.074 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:151645 |
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