The Function And Preliminary Mechanism Of Slc20a1b In Regulating The Hematopoietic Stem/Progenitor Cells Of Zebrafish

Hematopoietic process is complex and involved in the whole process of life.It is also closely related to various activities such as the aging,diseases and tumorigenesis of organisms.As the mature blood cells have short lifetime,hematopoietic stem/progenitor cells(HSPCs)need to be differentiated into multiple lineage progenitor cells and further form mature cells of various hematopoietic lineage.The hematopoietic stem cells(HSCs)is self-renewing,which provide great convenience for the clinical treatment of patients with hematopoietic diseases.HSPCs could be differentiated into lymphocyte progenitor cells,granulocyte progenitor cells,myeloid progenitor cells and megakaryocytic erythroid progenitor cells.These progenitor cells eventually differentiate into different mature blood cells,providing the entire hematopoietic system,capable of maintaining oxygen transport and immune-related functions.The production,maintenance,expansion,differentiation and maturation of HSPCs are regulated by a variety of genes and transcription factors.If HSCs are affected,causing their number or function to be abnormal,it would lead to many kinds of related diseases.Therefore,it is of great importance to deeply understand the development of HSCs and clarify the regulatory mechanism of differentiation,maturation and homeostasis maintenance of HSPCs.Zebrafish is an excellent model for studying organ development,human hereditary related diseases,hematopoietic development and hematological related diseases,for the genomes of zebrafish are highly similar and conservative to mammals.Therefore,by taking advantages of zebrafish in various aspects such as genetics,embryonic development and in vivo imaging,we hope to explore new mechanisms of developmental regulation in HSPCs,and to reveal the pathogenesis of related diseases and further provide insights into the clinical treatments.In the previous study of the laboratory,a mutant named smu07 was obtained through a large-scale forward genetic screening.We firstly identified the mutant gene to be slc20a1b by the positional cloning.Followed by using the CRISPR/Cas9 technology,the slc20a1b mutant was obtained,which could perfectly mimic the phenotype of smu07.Afterwards,we explored the hematopoietic phenotype of the smu07 mutant,and found that there was a developmental defect of HSPCs,which causes the mutation phenotype of smu07 in a cell-autonomous manner.Moreover,the smu07 mutant HSPCs showed both increased cell death and decreased cell proliferation at the same time.Finally,through the detection of the function of slc20a1b,we found that the defect of HSPCs was not caused by the potential changes in the transport function of phosphate cotransporters of slc20a1b.In conclusion,our study indicates that slc20a1b plays an important role in the early development of HSPCs.With a better understanding of the developmental regulatory network of HSPCs,it would be helpful to provide insights for the clinical treatment and drug screening of related blood diseases.