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Genome Res. 2015 Dec;25(12):1860-72. doi: 10.1101/gr.192237.115. Epub 2015 Oct 1.

Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells.

Author information

1
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
2
Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA;
3
Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA; Joslin Diabetes Center, Boston, Massachusetts 02215, USA;
4
Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA; Joslin Diabetes Center, Boston, Massachusetts 02215, USA; Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, Massachusetts 02115, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02140, USA;
5
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02140, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02140, USA.

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.

PMID:
26430063
PMCID:
PMC4665007
DOI:
10.1101/gr.192237.115
[Indexed for MEDLINE]
Free PMC Article

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