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

Kristina Kirschner, Tamir Chandra, Vladimir Yu Kiselev, David Flores-Santa Cruz, Iain C. Macaulay, Hyun Jun Park, Juan Li, David G. Kent, Rupa Kumar, Dean C. Pask, Tina L. Hamilton, Martin Hemberg, Wolf Reik, Anthony R. Green

Cell Reports · 2017 · ▲ 96 citations

Stem-cell exhaustion Altered intercellular communication Mouse

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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.

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Provenance

Source: OpenAlex
DOI: 10.1016/j.celrep.2017.04.074
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Fetched: 2026-06-11 MST

Cite this

APA

Kirschner, K., Chandra, T., Kiselev, V.Y., Cruz, D.F., Macaulay, I.C., Park, H.J., Li, J., Kent, D.G., Kumar, R., Pask, D.C., Hamilton, T.L., Hemberg, M., Reik, W., & Green, A.R. (2017). Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment. <em>Cell Reports</em>. https://doi.org/10.1016/j.celrep.2017.04.074

Vancouver

Kirschner K, Chandra T, Kiselev VY, Cruz DF, Macaulay IC, Park HJ, et al. Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment. Cell Reports. 2017. doi:10.1016/j.celrep.2017.04.074.

BibTeX

@article{kristina2017Prolif, title = {Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment}, author = {Kristina Kirschner and Tamir Chandra and Vladimir Yu Kiselev and David Flores-Santa Cruz and Iain C. Macaulay and Hyun Jun Park and Juan Li and David G. Kent and Rupa Kumar and Dean C. Pask and Tina L. Hamilton and Martin Hemberg and Wolf Reik and Anthony R. Green}, journal = {Cell Reports}, year = {2017}, doi = {10.1016/j.celrep.2017.04.074}, }