GSE134011
Urine-derived podocytes from Alport patients as a model for glomerular filtration barrier defects
Alport syndrome (AS) is a genetic defect involving mutations of collagen IV a3, a4 or a5 genes, resulting in distinctive clinical features: kidney disease, hearing loss and eye abnormalities. Podocytes are responsible of production and correct assembly of the collagen IV isoforms, however, specific alterations of podocyte phenotype are currently scarce. We here generated immortalised AS urine-derived podocyte from three different patients. AS podocytes expressed a typical podocyte signature when compared to normal urine-derived podocytes, with comparable expression of podocyte markers. Each AS cell line showed a collagen IV profile that reflected the typical patient mutation. Furthermore, by RNA-sequencing 348 genes were found differentially expressed in Alport podocytes. Gene Ontology analysis underlined enrichment in genes involved in cell motility, adhesion, survival and angiogenesis. In parallel, AS podocyte motility was reduced. In conclusion, our data clearly indicate that AS podocytes display altered features connected but distinct from the collagen alterations. Overall design: RNA-sequencing was performed on urine-derived podocytes from three Alport syndrome patients (three immortalized clones  for each patient) and one control healthy subject (three different passages): AS patient 1 (AS216P1, AS213P1, AS212P1: col4a3 mutation), AS patient 2 (AS612P2, AS611P2, AS610P2: col4a5 mutation), AS patient 3 (710P3, 71P3, 72P3: col4a5 mutation), Urine-derived podocytes (control). Total RNA isolated from control podocytes and AS podocyte cell lines.