Deletion of hepcidin disrupts iron homeostasis and hematopoiesis in zebrafish embryogenesis.

IF 3.7 2区生物学 Q1 DEVELOPMENTAL BIOLOGY

Development Pub Date : 2025-04-01 Epub Date: 2025-04-04 DOI:10.1242/dev.204307

Wenyi Yang, Mingjian Peng, Youquan Wang, Xiaowen Zhang, Wei Li, Xue Zhai, Zhichao Wu, Peng Hu, Liangbiao Chen

引用次数: 0

Abstract

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.

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Hepcidin缺失破坏斑马鱼胚胎发生中的铁稳态和造血。

铁是细胞生长和造血所必需的，受hepcidin （hamp）调节。然而，仓鼠在斑马鱼造血中的作用尚不清楚。在这里，我们使用Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated nuclease 9系统（CRISPR/Cas9系统）创建了一个稳定的hamp敲除斑马鱼模型。我们的研究表明，hamp缺失导致胚胎中母体铁超载，显著下调血红蛋白基因并降低血红蛋白含量。单细胞RNA测序鉴定了血液祖细胞的异常表达模式，其中一种特定的祖细胞亚型显示铁下垂增加和发育延迟。通过将hamp基因敲除的斑马鱼与gata1+细胞系（血细胞标记的鱼系）杂交，我们证实了血液祖细胞中的铁下垂。这些发现强调了hamp在铁调节和造血中的关键作用，为发育生物学和血液疾病的潜在治疗靶点提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Development 生物-发育生物学

CiteScore

6.70

自引率

4.30%

发文量

433

审稿时长

3 months

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