RUNX1-205, a novel splice variant of the human RUNX1 gene, has blockage effect on mesoderm-hemogenesis transition and promotion effect during the late stage of hematopoiesis

作     者：Wencui Sun Jiahui Zeng Jing Chang Yuan Xue Yonggang Zhang Xu Pan Ya Zhou Mowen Lai Guohui Bian Qiongxiu Zhou Jiaxing Liu Bo Chen Feng Ma Wencui Sun;Jiahui Zeng;Jing Chang;Yuan Xue;Yonggang Zhang;Xu Pan;Ya Zhou;Mowen Lai;Guohui Bian;Qiongxiu Zhou;Jiaxing Liu;Bo Chen;Feng Ma

作者机构：Institute of Blood TransfusionChinese Academy of Medical Sciences&Peking Union Medical College(CAMS&PUMC)Chengdu 610052China State Key Laboratory of BiotherapySichuan UniversityChengdu 61006China State Key Laboratory of Experimental HematologyCAMS&PUMCTianjin 300020China 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2020年第12卷第5期

页      面：386-396页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：supported by grants from the CAMS Initiatives for Innovative Medicine(2016-I2M-1-018 to F.M.and 2017-I2M-3-021 to J.L.) the Sichuan Provincial Health and Family Planning Commissi on research project(17PJ489 to B.C.) Chengdu Science and Technology Project-Technology Innovation R&D(2018-YF05-01341-SN to B.C.) 

主　　题：mesoderm-hemogenesis transition hematopoiesis hematopoietic stem/progenitor cells (HSPCs) RUNX1 mesoderm embryonic stem cells (ESCs) 

摘      要：Runt-related transcription factor 1(RUNX1)is required for definitive hematopoiesis;however,the functions of most human RUNX1 isoforms are *** particular,the effects of RUNX1-205(a novel splice variant that lacks exon 6 in comparison with RUNX1b)on human hematopoiesis are not *** this study,a human embryonic stem cell(hESC)line with inducible RUNX1-205 overexpression was *** of these cells revealed that induction of RUNX1-205 overexpression at early stage did not influence the induction of mesoderm but blocked the emergence of CD34+cells,and the production of hematopoietic stem/progenitor cells was significantly *** addition,the expression of hematopoiesis-related factors was ***,these effects were abolished when RUNX1-205 overexpression was induced after Day 6 in co-cultures of hESCs and AGM-S3 cells,indicating that the inhibitory effect occurred prior to generation of hemogenic endothelial cells,while the promotive effect could be observed during the late stage of *** is very similar to that of ***,the mRNA expression profile of RUNX1-205 during hematopoiesis was distinct from that of RUNX1b,and the protein stability of RUNX1-205 was much higher than that of ***,the function of RUNX1-205 in normal and diseased models should be further explored.