生物
Notch信号通路
细胞生物学
祖细胞
DNA甲基化
斑马鱼
造血
心理压抑
干细胞
遗传学
信号转导
基因
基因表达
作者
Yan Li,Chao Tang,Fan Liu,Caiying Zhu,Feng Liu,Ping Zhu,Lu Wang
出处
期刊:Development
[The Company of Biologists]
日期:2022-05-15
卷期号:149 (10)
被引量:2
摘要
ABSTRACT The earliest hematopoietic stem and progenitor cells (HSPCs) are generated from the ventral wall of the dorsal aorta, through endothelial-to-hematopoietic transition during vertebrate embryogenesis. Notch signaling is crucial for HSPC generation across vertebrates; however, the precise control of Notch during this process remains unclear. In the present study, we used multi-omics approaches together with functional assays to assess global DNA methylome dynamics during the endothelial cells to HSPCs transition in zebrafish, and determined that DNA methyltransferase 1 (Dnmt1) is essential for HSPC generation via repression of Notch signaling. Depletion of dnmt1 resulted in decreased DNA methylation levels and impaired HSPC production. Mechanistically, we found that loss of dnmt1 induced hypomethylation of Notch genes and consequently elevated Notch activity in hemogenic endothelial cells, thereby repressing the generation of HSPCs. This finding deepens our understanding of HSPC specification in vivo, which will provide helpful insights for designing new strategies for HSPC generation in vitro.
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