Hepcidin deletion disrupts iron homeostasis and hematopoiesis in zebrafish embryogenesis

Iron is essential for cell growth and hematopoiesis, regulated by hepcidin (hamp). However, hamp's role in zebrafish hematopoiesis remains unclear. Here, we created a stable hamp knockout zebrafish model using Clustered Regularly Interspaced Short Palindromic Repeats/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 hamp's critical role in iron regulation and hematopoiesis, offering novel insights into developmental biology and potential therapeutic targets for blood disorders.