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

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…

• HH
  Howard Hughes Medical Institute

  Award: P30-CA14051
• LA
  Leukemia and Lymphoma Society

  Awards: CA066996, P01 CA066996
• KF
  Klarman Family Foundation
• DC
  Dana-Farber Cancer Institute
• EH
  European Hematology Association
• KI
  Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

  Award: P30-CA14051
• FN
  Fundacja na rzecz Nauki Polskiej
• NI
  National Institutes of Health

  Awards: 1P50HG006193-01, 1P50HG006193, P30-CA14051, P01 CA066996, CA066996
• HS
  Harvard Stem Cell Institute
• NC
  National Cancer Institute

  Awards: P01 CA066996, CA066996, P30-CA14051, CA14051