The Study Of GFI1 In Myelopoiesis And The Establishment Of GFI1-related Myeloid Disease Models In Zebrafish

Myeloid cells are essential for immune function.Growth Factor Independence-1(GFI1),as a transcription factor,plays a key role in myeloid development,and its dysfunction can lead to a various of myeloid diseases,such as congenital neutropenia(SCN)and myelodysplastic syndrome(MDS).However,the effect of GFI1 on myeloid development is unclear,the further study of its effects on myeloid development is significant to improve the network of GFI1 regulating hematopoietic development.Zebrafish is an ideal model organism for studying hematopoietic development.There are two homologous genes of mammalian Gfi1 in zebrafish: gfi1 aa and gfi1 ab.In this paper,we explore the effects of Gfi1 aa and Gfi1 ab on myeloid development by using zebrafish.We observed the myeloid cells in the gfi1 aa mutant,and it was found that gfi1 aa affects embryonic neutrophil development,and we also found that Gfi1 aa maintains the normal development of neutrophil by inhibiting the expression of cebpa through genetics and molecular biology methods.Then we trace the pathological process of gfi1 aa mutants,and found that myelodysplasia,the proportion of blood cells in peripheral blood imbalanced,and symptoms worsened over time,similar to the phenotype of MDS patients.Next,we detected the effect of gfi1 ab on myeloid development and found that gfi1 ab deletion resulted in a reduction in macrophages and did not affect neutrophils.Finally,we examined the changes in myeloid cells in gfi1aa/gfi1 ab double mutants,and found that increased the number of neutrophils and decreased the number of macrophages in gfi1aa/gfi1 ab double mutants,indicating that gfi1 aa and gfi1 ab co-regulate myeloid cell developmental processes,and that gfi1aa/gfi1 ab double mutant similar to the phenotype of human SCN patients.In summary,on the one hand,this study revealed the Gfi1 aa maintains neutrophil development by targeting cebpa,and constructed a new zebrafish MDS-like disease model.On the other hand,we found that the gfi1aa/gfi1 ab double mutant is a SCN disease model.These results expand the understanding the role of GFI1 in myeloid development and its associated disease models will aid in the development of potential treatments for GFI1-related myeloid diseases.