Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells
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Kowalczyk-2015-Single-cell RNA-seq.pdf
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Author(s)
Kowalczyk, Monika S.
Tirosh, Itay
Heckl, Dirk
Rao, Tata Nageswara
Dixit, Atray
Haas, Brian J.
Schneider, Rebekka K.
Wagers, Amy J.
Ebert, Benjamin L.
Regev, Aviv
Date Issued
October 2015
Journal
Genome Research
Publisher
Cold Spring Harbor Laboratory Press
Citation
Kowalczyk, Monika S., Itay Tirosh, Dirk Heckl, Tata Nageswara Rao, Atray Dixit, Brian J. Haas, Rebekka K. Schneider, Amy J. Wagers, Benjamin L. Ebert, and Aviv Regev. “Single-Cell RNA-Seq Reveals Changes in Cell Cycle and Differentiation Programs Upon Aging of Hematopoietic Stem Cells.” Genome Res. 25, no. 12 (October 1, 2015): 1860–1872.
Version
Final published version
Abstract
Both intrinsic cell state changes and variations in the composition of stem cell populations have been implicated as contributors to aging. We used single-cell RNA-seq to dissect variability in hematopoietic stem cell (HSC) and hematopoietic progenitor cell populations from young and old mice from two strains. We found that cell cycle dominates the variability within each population and that there is a lower frequency of cells in the G1 phase among old compared with young long-term HSCs, suggesting that they traverse through G1 faster. Moreover, transcriptional changes in HSCs during aging are inversely related to those upon HSC differentiation, such that old short-term (ST) HSCs resemble young long-term (LT-HSCs), suggesting that they exist in a less differentiated state. Our results indicate both compositional changes and intrinsic, population-wide changes with age and are consistent with a model where a relationship between cell cycle progression and self-renewal versus differentiation of HSCs is affected by aging and may contribute to the functional decline of old HSCs.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1101/gr.192237.115
