Abstract：
:Regulated blood production is achieved through the hierarchical organization of dormant hematopoietic stem cell (HSC) subsets that differ in self-renewal potential and division frequency, with long-term (LT)-HSCs dividing the least. The molecular mechanisms underlying this variability in HSC division kinetics are unknown. We report here that quiescence exit kinetics are differentially regulated within human HSC subsets through the expression level of CDK6. LT-HSCs lack CDK6 protein. Short-term (ST)-HSCs are also quiescent but contain high CDK6 protein levels that permit rapid cell cycle entry upon mitogenic stimulation. Enforced CDK6 expression in LT-HSCs shortens quiescence exit and confers competitive advantage without impacting function. Computational modeling suggests that this independent control of quiescence exit kinetics inherently limits LT-HSC divisions and preserves the HSC pool to ensure lifelong hematopoiesis. Thus, differential expression of CDK6 underlies heterogeneity in stem cell quiescence states that functionally regulates this highly regenerative system.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Laurenti E,Frelin C,Xie S,Ferrari R,Dunant CF,Zandi S,Neumann A,Plumb I,Doulatov S,Chen J,April C,Fan JB,Iscove N,Dick JEdoi
10.1016/j.stem.2015.01.017subject
Has Abstractpub_date
2015-03-05 00:00:00pages
302-13issue
3eissn
1934-5909issn
1875-9777pii
S1934-5909(15)00018-1journal_volume
16pub_type
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