GATA2^(−/−) human ESCs undergo attenuatedendothelial to hematopoietic transition andthereafter granulocyte commitment

作     者：Ke Huang Juan Du Ning Ma Jiajun Liu Pengfei Wu Xiaoya Dong Minghui Meng Wenqian Wang Xin Chen Xi Shi Qianyu Chen Zhongzhou Yang Shubin Chen Jian Zhang Yuhang Li Wei Li Yi Zheng Jinglei Cai Peng Li Xiaofang Sun Jinyong Wang Duanqing Pei Guangjin Pan 

作者机构：CAS Key Laboratory of Regenerative BiologySouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Department of HematologySun Yat-sen UniversityGuangzhou 510630China South China University of TechnologyGuangzhou 510641China Key Laboratory for Major Obstetric Diseases of Guangdong ProvinceGuangzhouChina Key Laboratory of Reproduction and Genetics of Guangdong Higher Education InstitutesGuangzhouChina 

出 版 物：《Cell Regeneration》 (细胞再生（英文）)

年 卷 期：2015年第4卷第1期

页      面：32-46页

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：This work was supported by the following:National Basic Research Program of China,973 Program of China(2012CB966503,2011CB965204,2014CB964604) “Strategic Priority Research Program”of the Chinese Academy of Sciences Grant No.XDA01020202 National Natural Science Foundation of China(31371514,31200970,81301340) National Natural Science Foundation-Guangdong Joint Fund No.U1132005,National S&T Major Special Project on Major New Drug Innovation,Grant No.2011ZX09102010 “Hundred Talents Program”of Chinese Academy of Sciences(to Dr.G Pan) the Equipment Function Development&Technology Innovation Project of the Chinese Academy of Sciences(Grant Nos.yg2012049,yg2011082,and yg2011083) 

主　　题：hESCs GATA2 EHT HPC Granulocyte Notch signaling 

摘      要：Background: Hematopoiesis is a progressive process collectively controlled by an elaborate network of transcriptionfactors (TFs). Among these TFs, GATA2 has been implicated to be critical for regulating multiple steps of hematopoiesisin mouse models. However, whether similar function of GATA2 is conserved in human hematopoiesis, especially duringearly embryonic development stage, is largely ***: To examine the role of GATA2 in human background, we generated homozygous GATA2 knockout humanembryonic stem cells (GATA2^(−/−) hESCs) and analyzed their blood differentiation potential. Our results demonstratedthat GATA2^(−/−) hESCs displayed attenuated generation of CD34^(+)CD43^(+) hematopoietic progenitor cells (HPCs), due tothe impairment of endothelial to hematopoietic transition (EHT). Interestingly, GATA2^(−/−) hESCs retained the potentialto generate erythroblasts and macrophages, but never granulocytes. We further identified that SPI1 downregulationwas partially responsible for the defects of GATA2^(−/−) hESCs in generation of CD34^(+)CD43^(+) HPCs and ***, we found that GATA2^(−/−) hESCs restored the granulocyte potential in the presence of Notch ***: Our findings revealed the essential roles of GATA2 in EHT and granulocyte development throughregulating SPI1, and uncovered a role of Notch signaling in granulocyte generation during hematopoiesis modeled byhuman ESCs.