造血干细胞移植是治疗恶性血液病的有效手段，因此研究调控造血干祖细胞(HSPCs)定植过程的分子信号网络对提高骨髓移植效率等有重要意义。mDia1是哺乳动物中参与调控直链肌动蛋白微丝形成的Formin家族成员之一。mDia1缺失的小鼠髓系细胞产生骨髓增生异常综合症(MDS)病变，但mDia1缺失对MDS发病过程中HSPCs的功能是否存在影响尚不清楚。mDia蛋白可能存在功能上的互补，但缺乏直接的证据。本项目拟以基因敲除小鼠为材料，研究mDia1在HSPCs维持和骨髓移植中的功能；解析mDia1与mDia2可能存在的异源相互作用及其生化基础；探讨mDia1/mDia2协同调控造血干祖细胞功能的的分子机制。我们初步发现，mDia1缺失的HSPCs存在骨髓移植定植缺陷；mDia1与mDia2存在蛋白间相互作用；mDia1/mDia2双敲除小鼠出生后存在严重的存活缺陷，其HSPCs的发育受到抑制。

Hematopoietic stem cell transplantation is critical for the treatment of many malignant hematopoietic diseases. Therefore, the study of molecular signaling networks that regulate the engraftment of hematopoietic stem progenitor cells (HSPCs) is of great significance for improving the efficiency of bone marrow transplantation. mDia1 is one of the formin proteins in mammalian cells that modulates the linear actin polymerization. Loss of mDia1 led to myeloid dysplastic transformation of granulocytes in mice, however, its role in maintaining HSPCs homeostasis and functions in pathogenesis of MDS is largely unknown. Formin family proteins have potential redundant functions in vivo, but lack of direct evidence currently. The goal of this study is to elucidate the roles of mDia1 in HSPCs maintenance and bone marrow transplantation by utilizing multiple knockout mouse models. We also seek to analyze the potential protein-protein interaction between mDia1 and mDia2, and explore the molecular mechanisms of mDia1/mDia2 collaboratively regulating the function of HSPCs. Our preliminary results have suggested that inactivation of mDia1 in HSPCs caused engraftment defects during bone marrow transplantation. More importantly, mDia1 interacts with mDia2. The mDia1/mDia2 double knockout mice(DKO) have severe survival defects after birth, and the development of DKO HSPCs was largely impaired.