Kang Baoqiang, Zhang Tian, Huang Ke, Wang Tianyu, Li Yuhang, Mai Yuchan, Li Jinbing, Dang Shiying, Zhang Zhishuai, Huang Wenhao, Wang Junwei, Gao Minghui, Wang Yi, Pan Guangjin
Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun, China.
CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Cell Prolif. 2022 May;55(5):e13244. doi: 10.1111/cpr.13244. Epub 2022 May 3.
During embryonic haematopoiesis, haematopoietic stem/progenitor cells (HSPCs) develop from hemogenic endothelial cells (HECs) though endothelial to haematopoietic transition (EHT). However, little is known about how EHT is regulated in human. Here, we report that GFI1 plays an essential role in enabling normal EHT during haematopoietic differentiation of human embryonic stem cells (hESCs).
GFI1 deletion in hESCs leads to a complete EHT defect due to a closed chromatin state of hematopoietic genes in HECs. Mechanically, directly regulates important signaling pathways essential for the EHT such as PI3K signaling.etc.
Together, our findings reveal an essential role of GFI1 mediated epigenetic mechanism underlying human EHT during hematopoiesis.
在胚胎造血过程中,造血干/祖细胞(HSPCs)通过内皮向造血转化(EHT)从造血内皮细胞(HECs)发育而来。然而,关于人类中EHT如何被调控却知之甚少。在此,我们报告GFI1在人类胚胎干细胞(hESCs)造血分化过程中使正常EHT得以发生方面发挥着至关重要的作用。
hESCs中GFI1的缺失由于HECs中造血基因的染色质状态封闭而导致完全的EHT缺陷。从机制上讲,GFI1直接调节EHT所必需的重要信号通路,如PI3K信号通路等。
总之,我们的研究结果揭示了GFI1介导的表观遗传机制在人类造血过程中EHT的基础作用。