自噬
细胞生物学
造血
ATG5型
造血干细胞
核仁素
胚胎干细胞
生物
遗传学
干细胞
基因
细胞质
细胞凋亡
核仁
作者
Yumin Liu,Linjuan Shi,Yifan Chen,S.C. Luo,Yuehang Chen,H Chen,Wenlang Lan,Wenlang Lan,Zhan Yi Cao,Zehua Ye,Jinping Li,Bo Yu,Elaine Dzierzak,Zhuan Li
标识
DOI:10.1038/s41467-024-46453-y
摘要
Abstract An understanding of the mechanisms regulating embryonic hematopoietic stem cell (HSC) development would facilitate their regeneration. The aorta-gonad-mesonephros region is the site for HSC production from hemogenic endothelial cells (HEC). While several distinct regulators are involved in this process, it is not yet known whether macroautophagy (autophagy) plays a role in hematopoiesis in the pre-liver stage. Here, we show that different states of autophagy exist in hematopoietic precursors and correlate with hematopoietic potential based on the LC3-RFP-EGFP mouse model. Deficiency of autophagy-related gene 5 (Atg5) specifically in endothelial cells disrupts endothelial to hematopoietic transition (EHT), by blocking the autophagic process. Using combined approaches, including single-cell RNA-sequencing (scRNA-seq), we have confirmed that Atg5 deletion interrupts developmental temporal order of EHT to further affect the pre-HSC I maturation, and that autophagy influences hemogenic potential of HEC and the formation of pre-HSC I likely via the nucleolin pathway. These findings demonstrate a role for autophagy in the formation/maturation of hematopoietic precursors.
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