GATA2 −/− human ESCs undergo attenuated endothelial to hematopoietic transition and thereafter granulocyte commitment

• DOI: 10.1186/s13619-015-0018-7
• Publication Date: 2015-08-04T16:11:29Z
• Authors: 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
• Keywords: 0301 basic medicine; Medicine (General); QH301-705.5; Research; Granulocyte; EHT; 03 medical and health sciences; R5-920; hESCs; HPC; GATA2; Biology (General); Notch signaling

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