Cdk-inhibitors and exit from quiescence in primitive haematopoietic cell subsets.
Cdk-inhibitors and exit from quiescence in primitive haematopoietic cell subsets.
复制标题
Cdk 抑制剂并退出原始造血细胞亚群的静止状态。
DOI:
10.1046/j.1365-2141.2003.04780.x
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发表时间:
2004
影响因子:
6.5
通讯作者:
Watkins,SimonC
中科院分区:
文献类型:
--
作者:
Steinman,Richard;Yaroslavskiy,Beatrice;Goff,JulieP;Alber,SeanM;Watkins,SimonC
Prolonged quiescence of haematopoietic stem cells has been proposed to support durable haematopoiesis through clonal succession. Genetic experiments in mice have implicated the cyclin‐dependent kinase inhibitor (cdki) p21Waf1 in sustaining stem cell quiescence, and the cdki p27Kip1 in inhibiting the expansion of more mature progenitor cells. The expression of these inhibitory proteins in human haematopoietic stem cell candidates has not hitherto been studied. We describe a rare subpopulation (3 × 10−7umbilical cord mononuclear cells) of lineage‐negative cells that exhibited sustained resistance over months to cytokine‐induced cycling, and characterized the expression of p21Waf1 and p27Kip1 proteins in these cells. Whereas p27Kip1 was uniformly expressed in these cells, the expression of p21Waf1 in this population and in lineage‐negative CD34+cells was variable. For this rare subset of cells exhibiting prolonged quiescence, p21Waf1 may be dispensable and p27Kip1 necessary for growth arrest.