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 t...

Full description

Bibliographic Details
Main Authors: Kowalczyk, Monika S. (Author), Tirosh, Itay (Author), Heckl, Dirk (Author), Rao, Tata Nageswara (Author), Dixit, Atray (Author), Haas, Brian J. (Author), Schneider, Rebekka K. (Author), Wagers, Amy J. (Author), Ebert, Benjamin L. (Author), Regev, Aviv (Contributor)
Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor)
Format: Article
Language:English
Published: Cold Spring Harbor Laboratory Press, 2016-04-19T16:40:56Z.
Subjects:
Online Access:Get fulltext
LEADER 02365 am a22003253u 4500
001 102261
042 |a dc 
100 1 0 |a Kowalczyk, Monika S.  |e author 
100 1 0 |a Massachusetts Institute of Technology. Department of Biology  |e contributor 
100 1 0 |a Regev, Aviv  |e contributor 
700 1 0 |a Tirosh, Itay  |e author 
700 1 0 |a Heckl, Dirk  |e author 
700 1 0 |a Rao, Tata Nageswara  |e author 
700 1 0 |a Dixit, Atray  |e author 
700 1 0 |a Haas, Brian J.  |e author 
700 1 0 |a Schneider, Rebekka K.  |e author 
700 1 0 |a Wagers, Amy J.  |e author 
700 1 0 |a Ebert, Benjamin L.  |e author 
700 1 0 |a Regev, Aviv  |e author 
245 0 0 |a Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells 
260 |b Cold Spring Harbor Laboratory Press,   |c 2016-04-19T16:40:56Z. 
856 |z Get fulltext  |u http://hdl.handle.net/1721.1/102261 
520 |a 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. 
520 |a Howard Hughes Medical Institute 
520 |a National Institutes of Health (U.S.) (Centers of Excellence in Genomic Science Award 1P50HG006193-01) 
520 |a National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051) 
520 |a Klarman Cell Observatory 
546 |a en_US 
655 7 |a Article 
773 |t Genome Research