Molecular characterization of clonal human renal forming cells

The adult kidney replaces lost cells in-vivo via proliferation of cells functioning as committed clonal progenitors. Here we combined the generation of single cell derived clonal cultures from human adult kidney with transcriptomic analysis for molecular characterization of in-vitro clonal behavior at inception and after propagation. We discovered two types of clones; rapidly proliferating de-differentiated fibroblast-like (FL) originating from the proximal tubule and stably proliferating cuboidal epithelial-like (EL) originating from distal segments that efficiently propagate with one cell giving rise to 3.3*10(6) cells. Segment-specific clonal heterogeneity included molecular characteristics of cell-cycle, epithelial-mesenchymal transition (high NCAM1, Serpine1) and oxidative phosphorylation in FL-clones. In contrast, the more quiescent EL-clones harboring markers of mature kidney epithelia (high CD24, CDH1/E-cad, EpCAM) activate the BMP pathway.  Thus, the human adult kidney harbors progenitor cell function in which segment identity and the level of epithelial maturation dictate clonal behavior and sustained renal cell formation in culture. RNA-Sequencing of 9 hAK (human adult kidney) clones in early or late passage. Bulk hAK cultures were used as control