p21/Zbtb18 repress the expression of cKit to regulate the self-renewal of hematopoietic stem cells  

作　　者：Nini Wang Shangda Yang Yu Li Fanglin Gou Yanling Lv Xiangnan Zhao Yifei Wang Chang Xu Bin Zhou Fang Dong Zhenyu Ju Tao Cheng Hui Cheng 

机构地区：[1]State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Haihe Laboratory of Cell Ecosystem,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China [2]CAMS Center for Stem Cell Medicine,PUMC Department of Stem Cell and Regenerative Medicine,Tianjin 300020,China [3]The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics,Key Laboratory of Immune Microenvironment and Disease(Ministry of Education),Department of Cell Biology,Tianjin Medical University,Tianjin 300270,China [4]State Key Laboratory of Cell Biology,Shanghai Institute of Biochemistry and Cell Biology,Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai 200031,China [5]Key Laboratory of Regenerative Medicine of Ministry of Education,Institute of Aging and Regenerative Medicine,College of Life Science and Technology,Jinan University,Guangzhou 510632,China

出　　处：《Protein & Cell》2024年第11期840-857,共18页蛋白质与细胞（英文版）

基　　金：supported by grants from the Ministry of Science and Technology of China(2021YFA1100900,2020YFE0203000,2021YFA1100103);the National Natural Science Foundation of China(92368202,82270120,82222004,82230047);the Haihe Laboratory of Cell Ecosystem Innovation Fund(22HHXBSS00016);the CAMS Initiative for Innovative Medicine(2021-I2M-1-019 and 2022-I2M-2-001);the CAMS Fundamental Research Funds for Central Research Institutes(3332021093);the Distinguished Young Scholars of Tianjin(23JCJQJC00220).

摘　　要：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.

关 键 词：hematopoietic stem cells SELF-RENEWAL P21 Zbtb18 cKit 

分 类 号：Q343[生物学—遗传学]