GSE128736
Glomerular endothelial cell mRNA profiles in mice with podocyte depletion
we profiled GEC mRNA expression levels in two animal models with podocyte depletion. We used a transgenic mouse model with YFP-labelled GEC for sorting of GEC. Podocyte depletion was induced by injection of mice with a specific anti-podocyte antibody or crossing with a podocyte-specific doxycycline-induced diphtheria toxin A (DTA) expression transgenic mouse model. Both mouse models developed significant proteinuria, glomerulosclerosis, and podocyte depletion.  YFP-positive GECs were sorted from these mice for RNA sequencing. Analysis of the differentially expressed genes (DEGs) between the diseased and control mice revealed significant alteration of metabolism and immune system in the antibody-mediated podocyte depletion model while angiogenesis, vascular development, actin cytoskeleton, and focal adhesion pathways were highly enriched in the DTA model. Apoptosis and cell adhesion pathways were enriched in both models. Apoptosis of GEC was confirmed in the kidney of these mice, which leads to the reduction of GEC number. We also identified a list of genes which were altered in both animal models. Among them, we have further validated Cd63, a molecule which is regulated in human DKD and plays a key role in endothelial cell function. In conclusion, this is the first unbiased approach to determine the genomic-wide response of GEC to podocyte depletion in two different animal models. Our study proves that podocyte depletion could induce GEC injury. Overall design: Podocyte depletion was induced by injection of mice with a specific anti-podocyte antibody or crossing with a podocyte-specific doxycycline-induced diphtheria toxin A (DTA) expression transgenic mouse model. YFP-positive GECs were sorted from these mice for RNA sequencing ***Please note that GSE128736 is incorrectly cited for Diabetes 2019, PMID: 31578193***