GSE218376 Spatiotemporal landscape of kidney tubular responses to glomerular proteinuria

Contributors : Anna Faivre ; Milica Bugarski ; Anna Rinaldi ; Thomas Verissimo ; Imene B Sakhi ; David Legouis ; Sara Correia ; Monika Kaminska ; Delal Dalga ; Pietro E Cipp à ; Sophie de Seigneux ; Andrew HallSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusProteinuria is a cardinal feature of glomerular diseases and an important risk factor for tubulo-interstitial damage, progressive decline in kidney function, and cardiovascular complications, but the precise effects of proteinuria on tubules were previously unclear. Here, using an established mouse model of glomerulopathy, single cell sequencing, in vivo imaging and other complementary methods, we investigate in detail the spatiotemporal landscape of genetic responses to increased protein filtration along the nephron. We show that proteinuria is a potent modulator of cell signaling in tubules, and triggers extensive genetic reprogramming in distal segments, with activation of numerous developmental pathways, and a generalized convergence and loss of differentiation markers. Meanwhile, in the proximal tubule - where filtered proteins are normally endocytosed and degraded - we find that encroachment of protein uptake from early (S1) into later (S2) segments causes substantial remodeling of the latter, with dramatic downregulation of canonical processes such as organic anion/uremic toxin secretion and lipid metabolism, and a concomitant increase in reabsorptive markers. Thus, ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research