Congenital asplenia impairs heme-iron recycling during erythropoiesis in zebrafish

In this study, HSC-regulated and erythrocyte marker genes, such as gata1a, gata2, klf1, hbaa1, hbaa2, hbba1 and hbba2 were significantly reduced in congenitally asplenic zebrafish when compared with wild-type (WT). Subsequently, we conducted the transcriptome profiles of whole kidneys from WT and congenitally asplenic zebrafish to explore the possible molecular mechanisms underlying the impaired erythropoiesis caused by congenital asplenia. Our results demonstrated that congenital asplenia might impair heme-iron recycling during erythropoiesis, as evidenced by significant down-regulation of genes associated with iron acquisition (tfr1a, tfa, steap3 and slc25a37) and heme biosynthesis and transport (alas2, fech, uros, urod, copx, ppox and abcb10) in congenitally asplenic zebrafish. In addition, the down-regulation of hemopoiesis-related GO terms, including heme binding, tetrapyrrole binding, iron ion binding, heme metabolic process, heme biosynthetic process, erythrocyte differentiation, iron ion homeostasis and hemoglobin metabolic process confirmed the impaired erythropoiesis induced by congenital asplenia. Our study provides an in-depth understanding of spleen function in regulating heme-iron homeostasis during hematopoiesis, thereby providing valuable insights into pathological responses in splenectomized or congenitally asplenic patients.PMID:38040044 | DOI:10.1016/j.dci.2023.105108
Source: Developmental and Comparative Immunology - Category: Allergy & Immunology Authors: Source Type: research