RT Journal
A1 Kowalczyk, Monika S.
A1 Tirosh, Itay
A1 Heckl, Dirk
A1 Rao, Tata Nageswara
A1 Dixit, Atray
A1 Haas, Brian J.
A1 Schneider, Rebekka K.
A1 Wagers, Amy J.
A1 Ebert, Benjamin L.
A1 Regev, Aviv
T1 Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells
JF Genome Research 
JO Genome Research 
YR 2015 
FD December 01 
VO 25 
IS 12 
SP 1860 
OP 1872 
DO 10.1101/gr.192237.115 
UL http://genome.cshlp.org/content/25/12/1860.abstract 
AB 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.