Cyclin C regulates human hematopoietic stem/progenitor cell quiescence.

Cyclin C regulates human hematopoietic stem/progenitor cell quiescence.
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DOI:
10.1002/stem.270
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发表时间:
2010-02
期刊:
影响因子:
5.2
通讯作者:
Nimer, Stephen D.
Nimer, Stephen D.
中科院分区:
医学2区
文献类型:
--
作者:
Miyata, Yasuhiko;Liu, Yan;Jankovic, Vladimir;Sashida, Goro;Lee, Jennifer May;Shieh, Jae-Hung;Naoe, Tomoki;Moore, Malcolm;Nimer, Stephen D.

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造血干细胞(HSCs)可以保持静止状态,也可以进入细胞周期,并自我更新或分化。细胞周期蛋白C和cdk3是人成纤维细胞周期从G0期向G1期转变所必需的,但细胞周期蛋白C在造血干/祖细胞中的作用尚不清楚。我们发现细胞周期蛋白C(Cyclin C,CCNC)在调节人HSPC静止状态中起着重要作用,因为下调人脐血CD34+细胞中细胞周期蛋白C的表达会导致维持CD34表达的静止期细胞显著增加。Ccnc基因敲除也促进了HSPC的体外扩增,并增强了它们在亚致死剂量辐射免疫缺陷小鼠中的植入潜力。我们的研究证实细胞周期蛋白C是人类造血干细胞G0/G1转变的关键调节因子,并提示调节细胞周期蛋白C水平可能有助于造血干细胞的扩增和更有效的植入。
Hematopoietic stem cells (HSCs) can remain quiescent or they can enter the cell cycle, and either self-renew or differentiate. While cyclin C and cdk3 are essential for the transition from the G0 to G1 phase of the cell cycle in human fibroblasts, the role of cyclin C in hematopoietic stem/progenitor cells (HSPCs) is not clear. We have identified an important role of cyclin C (CCNC) in regulating human HSPC quiescence, as knocking down CCNC expression in human cord blood (CB) CD34+ cells resulted in a significant increase in quiescent cells that maintain CD34 expression. CCNC knockdown also promotes in vitro HSPC expansion and enhances their engraftment potential in sub-lethally irradiated immunodeficient mice. Our studies establish cyclin C as a critical regulator of the G0/G1 transition of human HSPCs and suggest that modulating cyclin C levels may be useful for HSC expansion and more efficient engraftment.
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