PDGFR α^+细胞来源的SCF对小鼠成体造血的调控作用

PDGFR α^+ Cell-Derived SCF Regulates Hematopoiesis of Adult Mice

目的:探究PDGFRα+基质细胞来源的SCF对小鼠成体造血的影响。方法:构建Pdgfrα-CreER;tdTomato小鼠,应用流式细胞术和共聚焦显微镜分析该模型小鼠的肝脏、脾脏、肺脏、肾脏和骨髓中PDGFRα+细胞的比例和分布情况;构建Pdgfrα-CreER;Scfflox/flox条件性敲除小鼠,在PDGFRα+基质细胞中特异敲除Scf,采用流式细胞术检测敲除Scf对小鼠骨髓造血干/祖细胞(HSPC)比例的影响;通过全血细胞分析仪分析SCF对小鼠外周血细胞比例和数目的影响。结果:在PDGFRα+细胞中敲除Scf后,小鼠骨髓LKS-、LKS+、HSC、MPP1、MKP、PreGM、PreMegE、CFU-E细胞比例、数目减少;外周血红细胞数目、血红蛋白浓度下降。然而,在PDGFRα+细胞中敲除Scf对脾脏造血没有影响。结论:在小鼠成体造血过程中,特异敲除PDGFRα+细胞Scf会降低骨髓中HSPC的比例和外周血中红细胞数量,导致小鼠出现贫血状况。

Objective:To investigate the effect of PDGFRα+stromal cells derived SCF on hematopoiesis of adult mice.Methods:Pdgfrα-CreER;R26-tdTomato mice model was constructed,and the proportion and distribution of PDGFRα+cells in the liver,spleen,lung,kidney and bone marrow were analyzed by flow cytometry and confocal microscopy.Then the Pdgfrα-CreER;Scfflox/flox mice model was further constructed,the Scf in PDGFRα+was knocked out specifically,the effect of Scf-knocked out in PDGFRα+stromal cells in the propitiation of HSPCs in the bone marrow was analyzed by flow cytometry.The effect of SCF on the proportion on number of peripheral blood cells in mice was analyzed by whole blood analyzer.Results:After Scf was knocked out in PDGFRα+stromal cells,the propitiation and number of LKS-cell,LKS+cell,HSC,MPP1,MKP,PreGM,PreMegE,and CFU-E in the bone marrow of mice was decreased,as well as in the number of red blood cells and hemoglobin concentration of peripheral blood.However,Scf knocked out from PDGFRα+cells showed no effect on the hematopoiesis in spleen.Conclusion:specific knocked out of Scf in PDGFRα+stromal cells in adult mice can decrease the proportion of HSPCs in the bone marrow and the number of red blood cells in peripheral blood,and finally lead to anemia in mice.