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

Author:

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

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.

Funder

European Hematology Association

EMBO Long Term Fellowship

HFSP Long Term Fellowship

Rothschild Fellowship

German Cancer Foundation

Leukemia and Lymphoma Society

National Institutes of Health

HHMI

NIH CEGS

Klarman Family Foundation

Howard Hughes Medical Institute

Publisher

Cold Spring Harbor Laboratory

Subject

Genetics(clinical),Genetics

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