Overexpression of HOXA9 upregulates NF-κB signaling to promote human hematopoiesis and alter the hematopoietic differentiation potentials  

作　　者：Jiahui Zeng Danying Yi Wencui Sun Yuanlin Liu Jing Chang Lijiao Zhu Yonggang Zhang Xu Pan Yong Dong Ya Zhou Mowen Lai Guohui Bian Qiongxiu Zhou Jiaxin Liu Bo Chen Feng Ma 

机构地区：[1]Chinese Academy of Medical Sciences&Peking Union Medical College(CAMS&PUMC),Institute of Blood Transfusion,No.26,Huacai Road,Longtan Industry Park,Chenghua District,Chengdu 610052,China [2]State Key Laboratory of Biotherapy,Sichuan University,Chengdu 610065,China [3]State Key Laboratory of Experimental Hematology,CAMS&PUMC,Tianjin 300020,China

出　　处：《Cell Regeneration》2021年第1期95-106,共12页细胞再生（英文）

基　　金：This work was supported by awards from the CAMS Initiatives for Innovative Medicine(2016-I2M-1-018 to F.Ma and 2017-I2M-3-021 to J.X.Liu);Sichuan Provincial Science and Technology Department Key R&D projects(020YFSY0023 to B.Chen);the Chengdu Science and Technology Project-Technology Innovation R&D(2018-YF05-01341-SN to B.Chen).

摘　　要：Background: The HOX genes are master regulators of embryogenesis that are also involved inhematopoiesis. HOXA9 belongs to a cluster of HOX genes that play extensively studied roles inhematopoiesis and leukemogenesis.Methods: We established HOXA9-inducible human embryonic stem cells (HOXA9/hESCs) with normalpluripotency and potential for hematopoiesis, which could be used to analyze gene function with highaccuracy. HOXA9/hESCs co-cultured with aorta–gonad–mesonephros-derived stromal cells (AGM-S3) wereinduced to overexpress HOXA9 with doxycycline (DOX) at various times after hematopoiesis started andthen subjected to flow cytometry.Results: Induction of HOXA9 from Day 4 (D4) or later notably promoted hematopoiesis and also increasedthe production of CD34+ cells and derived populations. The potential for myelogenesis was significantlyelevated while the potential for erythrogenesis was significantly reduced. At D14, a significant promotion ofS phase was observed in green fluorescent protein positive (GFP+) cells overexpressing HOXA9. NF-κBsignaling was also up-regulated at D14 following induction of HOXA9 on D4. All of these effects could becounteracted by addition of an NF-κB inhibitor or siRNA against NFKB1 along with DOX.Conclusions: Overexpression of HOXA9 starting at D4 or later during hematopoiesis significantly promotedhematopoiesis and the production of myeloid progenitors while reduced the production of erythroidprogenitors, indicating that HOXA9 plays a key role in hematopoiesis and differentiation of hematopoieticlineages.

关 键 词：HEMATOPOIESIS Differentiation of hematopoietic lineages HOXA9 MESODERM Human embryonic stem cells(hESCs) TET-ON Inducible expression system 

分 类 号：R73[医药卫生—肿瘤]