GENERATION OF RENAL EPITHELIAL CELL DIVERSITY

肾功能依赖于正确的关联和排列 至少14种独特的上皮细胞类型向肾小球和 管状节段。这些异型细胞类型是从 胚胎后肾中存在未分化的间充质细胞 肾原基。间充质细胞可能是产生ALL的干细胞 肾细胞类型或间充质细胞可能是一组不同类型的 每个细胞直接分化成独特的肾脏细胞类型。至 区分这些模型，lac-Z基因被引入到 单个间充质细胞(大鼠，妊娠13周) 鉴定了复制缺陷逆转录病毒及其后代 在体外分化后。标记个体的无性系后代 细胞分布于肾小球和近端小管段。 单肾单位。这些结果表明，后肾 间充质含有多能的肾干细胞。一座图书馆 干细胞特异性的单抗将被制备来表征 这种新鉴定的干细胞，曾经跟随它的命运 差异化。将定义细胞培养条件，以支持 这些干细胞的增殖。此外，这些细胞将是 永生化和克隆细胞系的建立。这些试剂和细胞 将使用线条来识别和描述监管机制 介导未分化间充质细胞转化为 肾上皮细胞类型多样。

Renal function is dependent on the correct association and alignment of at least 14 unique transporting epithelial cell types into glomerular and tubular segments. These hetrrogeneous cell types are derived from the undifferentiated mesenchymal cells present in the embryonic metanephric kidney anlage. Mesenchymal cells could be stem cells that generate all renal cell types or mesenchymal ells might be a heterogeneous group of cells each differentiating directly into unique renal cell types. To distinguish between these models, the lac-Z gene was introduced into individual mephrogenic mesenchymal cells (rat, gestation cay 13) using replication defective retroviruses and their progeny were identified after differentiation in vitro. The clonal progeny of individual tagged cells were found to reside in glomerulus and proximal tubule segments of single nephron. These results demonstrate that the metanephric mesenchyme contains multipotent nephrogenic stem cells. A library of stem ell specific monoclonal antibodies will be prepared to characterize this newly ientified stem cell, and used to follow its fate during differentiation. Cell culture conditions will be defined that support the proliferation of these stem cells. In addition these cells will be immortalized and clonal cell lines established. These reagents and cell lines will be used to identify and characterize the regulatory mechanisms mediating the conversion of an undifferentiated mesenchymal cell into diverse renal epithelial celll types.