PUBLICATION

Hepcidin deletion disrupts iron homeostasis and hematopoiesis in zebrafish embryogenesis

Authors
Yang, W., Peng, M., Wang, Y., Zhang, X., Li, W., Zhai, X., Wu, Z., Hu, P., Chen, L.
ID
ZDB-PUB-250321-1
Date
2025
Source
Development (Cambridge, England) : (Journal)
Registered Authors
Chen, Liangbiao
Keywords
hamp, Hematopoiesis, Single cell transcriptomics, Zebrafish
MeSH Terms
  • Animals
  • CRISPR-Cas Systems/genetics
  • Iron*/metabolism
  • Embryo, Nonmammalian/metabolism
  • Hepcidins*/genetics
  • Hepcidins*/metabolism
  • Gene Expression Regulation, Developmental
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • GATA1 Transcription Factor/genetics
  • GATA1 Transcription Factor/metabolism
  • Hematopoiesis*/genetics
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Embryonic Development*/genetics
  • Ferroptosis/genetics
  • Homeostasis*/genetics
  • Gene Deletion
  • Gene Knockout Techniques
PubMed
40110772 Full text @ Development
Abstract
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping