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 

机构地区：[1]Institute of Blood Transfusion,Chinese Academy of Medical Sciences&Peking Union Medical College(CAMS&PUMC),Chengdu 610052,China [2]State Key Laboratory of Biotherapy,Sichuan University,Chengdu 61006,China [3]State Key Laboratory of Experimental Hematology,CAMS&PUMC,Tianjin 300020,China

出　　处：《Journal of Molecular Cell Biology》2020年第5期386-396,共11页分子细胞生物学报（英文版）

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.).

摘　　要：Runt-related transcription factor 1(RUNX1)is required for definitive hematopoiesis;however,the functions of most human RUNX1 isoforms are unclear.In particular,the effects of RUNX1-205(a novel splice variant that lacks exon 6 in comparison with RUNX1b)on human hematopoiesis are not clear.In this study,a human embryonic stem cell(hESC)line with inducible RUNX1-205 overexpression was established.Analyses 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 reduced.In addition,the expression of hematopoiesis-related factors was downregulated.However,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 hematopoiesis.This is very similar to that of RUNX1b.Interestingly,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 RUNX1b.Thus,the function of RUNX1-205 in normal and diseased models should be further explored.

关 键 词：mesoderm-hemogenesis TRANSITION HEMATOPOIESIS hematopoietic stem/progenitor CELLS (HSPCs) RUNX1 MESODERM embryonic STEM CELLS (ESCs) 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]