PUBLICATION

Genetic and epigenetic orchestration of Gfi1aa-Lsd1-cebpα in zebrafish neutrophil development

Authors
Wu, M., Xu, Y., Li, J., Lian, J., Chen, Q., Meng, P., Lu, T., Xie, H., Zhang, W., Xu, J., Zhang, Y.
ID
ZDB-PUB-210811-9
Date
2021
Source
Development (Cambridge, England)   148(17): (Journal)
Registered Authors
Zhang, Wenqing, Zhang, Yiyue
Keywords
Gfi1aa, Lsd1, Neutrophil differentiation, Zebrafish, cebpα
Datasets
GEO:GSE182346
MeSH Terms
  • Animals
  • CCAAT-Enhancer-Binding Proteins/genetics
  • CCAAT-Enhancer-Binding Proteins/metabolism*
  • Cell Differentiation
  • Cell Proliferation
  • DNA-Binding Proteins/deficiency
  • DNA-Binding Proteins/metabolism*
  • Embryo, Nonmammalian
  • Epigenesis, Genetic
  • Granulocyte Precursor Cells/cytology
  • Granulocyte Precursor Cells/metabolism
  • Hematopoiesis/genetics*
  • Histone Demethylases/genetics
  • Histone Demethylases/metabolism*
  • Neutrophils/cytology*
  • Neutrophils/metabolism
  • Zebrafish
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
34373913 Full text @ Development
Abstract
Neutrophils are the most abundant vertebrate leukocytes and they are essential to host defense. Despite extensive investigation, the molecular network controlling neutrophil differentiation remains incompletely understood. GFI1 is associated with several myeloid disorders, but its role and the role of its co-regulators in granulopoiesis and pathogenesis are far from clear. Herein, we demonstrate that zebrafish gfi1aa deficiency induces excessive neutrophil progenitor proliferation, accumulation of immature neutrophils from the embryonic stage, and some phenotypes similar to myelodysplasia syndrome in adulthood. Both genetic and epigenetic analysis demonstrated immature neutrophil accumulation in gfi1aa-deficient mutants to be due to up-regulation of cebpα transcription. Increased transcription was associated with Lsd1 altered H3K4 methylation of cebpα regulatory region. Taken together, results demonstrated Gfi1aa, Lsd1, and cebpα to form a regulatory network that controlled neutrophil development, providing a disease progression traceable model for myelodysplasia syndrome. The use of the model will provide new insights into a molecular understanding of GFI1 related myeloid disorders as well a mean by which to develop targeted therapeutic approaches for treatment.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes