CDK6 levels regulate quiescence exit in human hematopoietic stem cells.
Cell Stem Cell
; 16(3): 302-13, 2015 Mar 05.
Article
em En
| MEDLINE
| ID: mdl-25704240
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Simulação por Computador
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Células-Tronco Hematopoéticas
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Regulação Enzimológica da Expressão Gênica
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Divisão Celular
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Quinase 6 Dependente de Ciclina
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Modelos Biológicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article