ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR155/083/SRR15509783/SRR15509783_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR155/082/SRR15509782/SRR15509782_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR155/083/SRR15509783/SRR15509783_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR155/081/SRR15509781/SRR15509781_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR155/084/SRR15509784/SRR15509784_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR155/081/SRR15509781/SRR15509781_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR155/082/SRR15509782/SRR15509782_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR155/084/SRR15509784/SRR15509784_1.fastq.gzprimaryOK200GenomicsZhang, School of Medicine, South China University of Technologyhttps://www.ebi.ac.uk/ena/browser/view/PRJNA755971Danio rerioNeutrophils 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. Overall design: Examination of Gfi1aa binding sites in zebrafish embryosxref:PubMed:34373913ENAzebra fish, DmelLSD1, polynuclear neutrophilic leukocyte, Band Cell, postnatal development., Lsd1, growth and development, LSD1, LSD1-like 1, Polymorphonuclear, lsd1, neutrophilic leucocyte, zebra danio, neutrophil leukocyte, CEBP, LE Cell, Cyprinus rerio, Dmel/LSD1, D. rerios, dLsd1, 1810043O07Rik, Neutrophil Band Cells, C/EBP, Suvar(3)3, AOF2, Aof2, SPK1, LYSINE-SPECIFIC HISTONE DEMETHYLASE, ATLSD1, ATSWP1, Zebrafishes, Cebp, neutrophil leucocyte, Fishes, neutrophilic leukocyte, Epigenomic, genetic, SWP1, C|ebpalpha, C/EBP alpha, Dmel/HDM, B. rerio, polymorphonuclear leukocyte, polynuclear neutrophilic leucocyte, Zebra Fishes, CBF-A, constitutitional genetic, LE, Su-var(3)3, Neutrophil, C/ebpalpha, Brachydanio rerio frankei, SU(VAR)3-3, xC/EBP, AA408884, C/EBP-alpha, leopard danio, Leukocyte, BHC110, Zebra Fish, F23N19.21, Polymorphonuclear Neutrophils, Leukocytes, DBPCEP, familial, F23N19_21, CG17149, Polymorphonuclear Leukocyte, Cell, Neutrophil Band Cell, development, neutrophil granulocyte, neutrocyte, mKIAA0601, DmelCG17149, LE Cells, Danio rerio frankei, Brachydanio rerio, KDM1, Kdm1, CEBPA, MEC2, Polymorphonuclear Neutrophil, Zebra, Danio rerio, neutrophilic granulocyte, Epigenetic, Danio frankei, Hdm, postnatal growth, C/EBPalpha, C|EBP-alpha, danio, ARABIDOPSIS LYSINE-SPECIFIC HISTONE DEMETHYLASE, Zebra danios, Zebra danio, D. rerio, Polymorphonuclear Leukocytes, PMN, polymorphonuclear leucocyte, inherited genetic, D4Ertd478e, Epigenetics, poly, hereditary, growth, saf110, zebrafish, polymorphonuclear neutrophil, swm1zebra fish, DmelLSD1, polynuclear neutrophilic leukocyte, Band Cell, postnatal development., Lsd1, growth and development, LSD1, LSD1-like 1, Polymorphonuclear, lsd1, neutrophilic leucocyte, zebra danio, neutrophil leukocyte, CEBP, LE Cell, Cyprinus rerio, Dmel/LSD1, D. rerios, dLsd1, 1810043O07Rik, Neutrophil Band Cells, C/EBP, Suvar(3)3, AOF2, Aof2, SPK1, LYSINE-SPECIFIC HISTONE DEMETHYLASE, ATLSD1, ATSWP1, Zebrafishes, Cebp, neutrophil leucocyte, Fishes, neutrophilic leukocyte, Epigenomic, genetic, SWP1, C|ebpalpha, C/EBP alpha, Dmel/HDM, B. rerio, polymorphonuclear leukocyte, polynuclear neutrophilic leucocyte, Zebra Fishes, CBF-A, constitutitional genetic, LE, Su-var(3)3, Neutrophil, C/ebpalpha, Brachydanio rerio frankei, SU(VAR)3-3, xC/EBP, AA408884, C/EBP-alpha, leopard danio, Leukocyte, BHC110, Zebra Fish, F23N19.21, Polymorphonuclear Neutrophils, Leukocytes, DBPCEP, familial, F23N19_21, CG17149, Polymorphonuclear Leukocyte, Cell, Neutrophil Band Cell, development, neutrophil granulocyte, neutrocyte, mKIAA0601, DmelCG17149, LE Cells, Danio rerio frankei, Brachydanio rerio, KDM1, Kdm1, CEBPA, MEC2, Polymorphonuclear Neutrophil, Zebra, Danio rerio, neutrophilic granulocyte, Epigenetic, Danio frankei, Hdm, postnatal growth, C/EBPalpha, C|EBP-alpha, danio, ARABIDOPSIS LYSINE-SPECIFIC HISTONE DEMETHYLASE, Zebra danios, Zebra danio, D. rerio, Polymorphonuclear Leukocytes, PMN, polymorphonuclear leucocyte, inherited genetic, D4Ertd478e, Epigenetics, poly, hereditary, growth, saf110, zebrafish, polymorphonuclear neutrophil, swm1falseGenetic and epigenetic orchestration of Gfi1aa-Lsd1-cebpa in zebrafish neutrophil developmentGenetic and epigenetic orchestration of Gfi1aa-Lsd1-cebpa in zebrafish neutrophil development2025-09-242021-08-23PRJNA755971GSE182346795534373913