造血
干细胞
生物
细胞生物学
基因敲除
转录因子
细胞周期
造血干细胞
下调和上调
转录调控
细胞生长
激酶
遗传学
细胞
细胞培养
基因
作者
N. Wang,Shangda Yang,Yu Liu,Fanglin Gou,Lv Y,Xiangnan Zhao,Yifei Wang,Chang Xu,Bin Zhou,Fang Dong,Zhenyu Ju,Tao Cheng,Hui Cheng
标识
DOI:10.1093/procel/pwae022
摘要
Abstract The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT− HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.
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