GENERATION OF RENAL EPITHELIAL CELL DIVERSITY

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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.