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,p2...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.展开更多
文摘目的 观察转录因子ZBTB18对结直肠癌细胞的生长的影响。方法 从NCBI GEO数据库中下载肿瘤基因表达芯片数据,对ZBTB18基因的表达水平进行分析;同时通过RNA干扰和Transwell实验研究ZBTB18对结直肠癌细胞迁移的影响。结果 ZBTB18蛋白表达于结直肠癌细胞系,且高转移能力的细胞系中该蛋白的表达水平远高于原发性结直肠癌肿瘤细胞系( P <0.05)。RNA干扰试验可特异性地显著沉默结直肠癌细胞HT29中ZBTB18的表达,Transwell实验发现在ZBTB18沉默后HT29细胞的侵袭和迁移能力显著降低( P <0.05)。结论 转录因子ZBTB18可以促进结直肠癌细胞的侵袭与迁移,可能参与结直肠癌的转移。
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)+3 种基金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).
文摘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.
