Iron is essential for cell growth and hematopoiesis, which is regulated by hepcidin (hamp). However, the role of hamp in zebrafish hematopoiesis remains unclear. Here, we have created a stable hamp knockout zebrafish model using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 system (CRISPR/Cas9 system). Our study revealed that hamp deletion led to maternal iron overload in embryos, significantly downregulating hemoglobin genes and reducing hemoglobin content. Single-cell RNA sequencing identified abnormal expression patterns in blood progenitor cells, with a specific progenitor subtype showing increased ferroptosis and delayed development. By crossing hamp knockout zebrafish with a gata1+ line (blood cells labeled fish line), we confirmed ferroptosis in blood progenitor cells. These findings underscore the crucial role of hamp in iron regulation and hematopoiesis, offering novel insights into developmental biology and potential therapeutic targets for blood disorders.

Author contributions

Investigation: W.Y., M.P., P.H.; Methodology: W.Y., X. Zhang, X. Zhai, Z.W.; Project administration: P.H., L.C.; Resources: L.C.; Visualization: M.P.; Writing - original draft: W.Y.; Writing - review & editing: P.H., L.C.; Funding acquisition: P.H.

Funding

This work was supported by the National Natural Science Foundation of China (32200414).

Data availability

The sequencing data generated in this study have been deposited in the NCBI BioProject database under accession number PRJNA1067370.

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