Tuning the 3D-microenvironment of reprogrammed tubule cells enhances biomimetic modeling of polycystic kidney disease.

Mutations in PKD1 cause Autosomal Dominant Polycystic Kidney Disease (ADPKD). To further investigate the impact of Pkd1 knockout on renal tubular cells, a direct reprogramming approach was applied. After direct reprogramming of mouse embryonic fibroblasts to induced renal tubular epithelial cells (iRECs), Pkd1 knockout iREC clones were generated by Cre-mediated recombination of floxed Pkd1 alleles. The knockout clones were compared to their corresponding wild type clones by RNA Sequencing and transcriptome profiling. Three knockout clones (Cre) were compared to their corresponding wild type clones (Flp): clone 4 Cre vs. Flp, clone 7 Cre vs. Flp, clone 21 Cre vs. Flp.