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Publication : Autophagy regulates the maturation of hematopoietic precursors in the embryo.

First Author  Liu Y Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  2255
PubMed ID  38490977 Mgi Jnum  J:346061
Mgi Id  MGI:7614133 Doi  10.1038/s41467-024-46453-y
Citation  Liu Y, et al. (2024) Autophagy regulates the maturation of hematopoietic precursors in the embryo. Nat Commun 15(1):2255
abstractText  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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