PUBLICATION

Sfxn1 is essential for erythrocyte maturation via facilitating hemoglobin production in zebrafish

Authors
Bao, B., An, W., Lu, Q., Wang, Y., Lu, Z., Tu, J., Zhang, H., Duan, Y., Yuan, W., Zhu, X., Jia, H.
ID
ZDB-PUB-210202-26
Date
2021
Source
Biochimica et biophysica acta. Molecular basis of disease   1867(5): 166096 (Journal)
Registered Authors
Jia, Haibo
Keywords
erythrocyte maturation, hemoglobin, mitochondrion, one-carbon metabolism, sfxn1, sideroblastic anemia
MeSH Terms
  • Anemia/metabolism
  • Anemia/pathology*
  • Animals
  • Cell Differentiation
  • Embryo, Nonmammalian/metabolism
  • Embryo, Nonmammalian/pathology*
  • Erythrocytes/metabolism
  • Erythrocytes/pathology*
  • Erythropoiesis
  • Hemoglobins/metabolism*
  • Mutation*
  • Phenotype
  • Sodium-Glucose Transporter 1/genetics
  • Sodium-Glucose Transporter 1/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
33524530 Full text @ BBA Molecular Basis of Disease
Abstract
Previous reports revealed that mutation of mitochondrial inner-membrane located protein SFXN1 led to pleiotropic hematological and skeletal defects in mice, associated with the presence of hypochromic erythroid cell, iron overload in mitochondrion of erythroblast and the development of sideroblastic anemia (SA). However, the potential role of sfxn1 during erythrocyte differentiation and the development of anemia, especially the pathological molecular mechanism still remains elusive. In this study, the correlation between sfxn1 and erythroid cell development is explored through zebrafish in vivo coupled with human hematopoietic cells assay ex vivo. Both knockdown and knockout of sfxn1 result in hypochromic anemia phenotype in zebrafish. Further analyses demonstrate that the development of anemia attributes to the biosynthetic deficiency of hemoglobin, which is caused by the biosynthetic disorder of heme that associates with one-carbon (1C) metabolism process of mitochondrial branch in erythrocyte. Sfxn1 is also involved in the differentiation and maturation of erythrocyte in inducible human umbilical cord blood stem cells. In addition, we found that functional disruption of sfxn1 causes hypochromic anemia that is distinct from SA. These findings reveal that sfxn1 is genetically conserved and essential for the maturation of erythrocyte via facilitating the production of hemoglobin, which may provide a possible guidance for the future clinical treatment of sfxn1 mutation associated hematological disorders.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping