RUNX1 overexpression triggers TGF-β signaling to upregulate p15 and thereby blocks early hematopoiesis by inducing cell cycle arrest

• DOI: 10.1016/j.scr.2022.102694
• Publication Date: 2022-01-31T08:36:03Z
• Authors: Wencui Sun; Danying Yi; Lijiao Zhu; Jiahui Zeng; Yuanling Liu; Jing Chang; Jiawen Teng; Yonggang Zhang; Yong Dong; Xu Pan; Yijin Chen; Ya Zhou; Mowen Lai; Qiongxiu Zhou; Jiaxin Liu; Bo Chen; Feng Ma
• Keywords: 0301 basic medicine; QH301-705.5; Tumor Suppressor Proteins; Cell Cycle; RUNX1/AML1; Cell Cycle Proteins; Cell Cycle Checkpoints; Cell cycle; P15; Hematopoiesis; 03 medical and health sciences; Transforming Growth Factor beta; Core Binding Factor Alpha 2 Subunit; Humans; Biology (General); TGF-β signaling pathway; Human embryonic stem cell (hESC); Cyclin-Dependent Kinase Inhibitor p16

p15INK4b (cyclin-dependent kinase inhibitor 2B, CDKN2B, p15), a cyclin-dependent (CKI) belonging to the INK4 family, plays an important role in hematopoiesis. Its expression level was positively related blockage effects of RUNX1b at early stage. Experiments using human embryonic stem cell (hESC) lines with inducible p15 suggested that overexpression can significantly decrease proportion KDR+ cells S and G2-M stages 4 days after induction from day 0. Moreover, stage production CD34highCD43- their derivative populations, but not CD34lowCD43- cells. These were weakened if delayed disappeared started 6. All these counteracted by inhibition TGF-β signaling. TGF-β1 stimulation elicited similar as overexpression. RUNX1 activation signaling pathway upregulate p15, which is partially responsible for blockade hematopoiesis relevant change cycle status. However, it possible other mechanisms are involved regulation