The Role Of MUS81 In Myeloid Progenitor Development

The mammalian blood system contains myeloid cells,erythrocytes,platelets,lymphocytes,megakary ocytes,mast cells,natural killer cells,and dendritic cells.Among them,granulocytes are involved in many responses,such as immune response,which is particularly important in the human body.Therefore,the regulation of granulocyte maturation and the differentiation are of great significance.Although there have been many scientific studies on granulocyte differentiation and development,the specific mechanism is still not clear.In order to explore the role of DNA damage repair protein MUS81 in the process of granulocyte differentiation,we firstly examined the expression of MUS81 protein in the process of granulocyte differentiation.Through immunofluorescence experiments,we found that MUS81 was specifically expressed at the lobulation of differentiated granular nuclei,but the expression of MUS81 disappeared at the end of differentiation and maturation.In order to study the regulatory role of MUS81 in granulocyte differentiation,we successfully constructed MUS81 conditioned knockout mice using CRISPR-Cas9 technology.By comparing the hematopoietic related cells of wildetype mice and Mus81 knockout mice,we found that there was no significant difference in the proportion of cells in the peripheral blood of each line.There was no significant difference in the proportion of each line of bone marrow primary cells and the proportion of hematopoietic progenitor cells.At the same time,we used shRNA technology to knock down Mus81 in human promyelocytic acute leukemia cell lines,and found that Mus81 gene knockout had no significant effect on granulocyte differentiation.In summary,single knockdown or deletion of MUS81 protein in human or mouse had no significant effect on the differentiation and maturation of granulocytes.In view of the important role of DNA damage repair in the hematopoietic process,we speculate that there may be a variety of compensatory mechanisms for DNA damage repair in the process of granulocyte differentiation and maturation.