期刊
GENOME RESEARCH
卷 25, 期 12, 页码 1860-1872出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.192237.115
关键词
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资金
- European Hematology Association
- EMBO Long Term Fellowship
- Foundation for Polish Science
- HFSP Long Term Fellowship
- Rothschild Fellowship
- German Cancer Foundation
- Leukemia and Lymphoma Society Scholar Award
- National Institutes of Health (NIH) [P01 CA066996]
- HHMI
- NIH CEGS Award [1P50HG006193-01]
- Koch Institute Support (core) Grant from the National Cancer Institute [P30-CA14051]
- Klarman Family Foundation
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 GI phase among old compared with young long-term HSCs, suggesting that they traverse through a 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 selfrenewal versus differentiation of HSCs is affected by aging and may contribute to the functional decline of old HSCs.
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