Autophagy regulates the maturation of hematopoietic precursors in the embryo

Yumin Liu, Linjuan Shi, Yifan Chen, Sifan Luo, Yuehang Chen, Hongtian Chen, Wenlang Lan, Xun Lu, Zhan Cao, Zehua Ye, Jinping Li, Bo Yu, Elaine Dzierzak and Zhuan Li ()
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Yumin Liu: Southern Medical University
Linjuan Shi: Southern Medical University
Yifan Chen: Southern Medical University
Sifan Luo: Southern Medical University
Yuehang Chen: Southern Medical University
Hongtian Chen: Southern Medical University
Wenlang Lan: Southern Medical University
Xun Lu: Southern Medical University
Zhan Cao: Southern Medical University
Zehua Ye: Southern Medical University
Jinping Li: Southern Medical University
Bo Yu: Jinan University
Elaine Dzierzak: The University of Edinburgh
Zhuan Li: Southern Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-46453-y

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