Figure 1

Model-guided meta-analysis of ADPKD-responsive transcription identified consistent mis-regulation of 31 known and 61 new genes. Unbiased analysis of Pkd1- and Pkd2-dependent mRNA transcription in genome-edited renal tubular epithelial mIMCD3 ADPKD cells provided rich data with minimal variability. Core Pkd-dependent transcription was delineated by statistical analysis of differential gene expression and exploratory data simplification by principal component analysis. Function-based cluster analysis of identified regulation isolated key pathways caused by loss of Pkd genes. ADPKD disease-relevance was investigated by model-guided meta-analysis of Pkd1- and Pkd2-deficient cells and mice, as well as human PKD1−/− kidneys. Ultimately, integrative transcriptomics confirmed 31 previously described transcriptional regulations and identified 61 new genes transcriptionally regulated by both, PKD1 and PKD2.