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Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment
- Source :
- Kirschner, K, Chandra, T, Kiselev, V, Flores-Santa Cruz, D, Macaulay, I C, Jun Park, H, 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 ', Cell Reports . https://doi.org/10.1016/j.celrep.2017.04.074, Cell Reports, Vol 19, Iss 8, Pp 1503-1511 (2017), Cell Reports
- Publication Year :
- 2017
-
Abstract
- Summary 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.<br />Graphical Abstract<br />Highlights • Single-cell transcriptomics reveals functional decline in old HSCs • p53-associated functional decline is driven by prolonged proliferation • Subpopulation of HSCs show aging signature, revealing heterogeneity in the rate of aging<br />Kirschner et al. describe heterogeneous aging of hematopoietic stem cells (HSCs), with a subset of old HSCs displaying signs of functional exhaustion. An increase in proliferation expands the aged HSC subgroup, linking prolonged proliferation to functional decline in HSCs.
Details
- Language :
- English
- ISSN :
- 22111247
- Database :
- OpenAIRE
- Journal :
- Kirschner, K, Chandra, T, Kiselev, V, Flores-Santa Cruz, D, Macaulay, I C, Jun Park, H, 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 ', Cell Reports . https://doi.org/10.1016/j.celrep.2017.04.074, Cell Reports, Vol 19, Iss 8, Pp 1503-1511 (2017), Cell Reports
- Accession number :
- edsair.doi.dedup.....60d3695a633b40c444a9b434d42b1ecc
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.04.074