{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liu S"],"funding":["European Research Council","NIDDK NIH HHS","Universitätsklinikum Hamburg-Eppendorf (UKE)"],"pagination":["2"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9830686"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["<h4>Background</h4>Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and histopathologic glomerular lesions are among the earliest structural alterations of DN. However, the signaling pathways that initiate these glomerular alterations are incompletely understood.<h4>Methods</h4>To delineate the cellular and molecular basis for DN initiation, we performed single-cell and bulk RNA sequencing of renal cells from type 2 diabetes mice (BTBR ob/ob) at the early stage of DN.<h4>Results</h4>Analysis of differentially expressed genes revealed glucose-independent responses in glomerular cell types. The gene regulatory network upstream of glomerular cell programs suggested the activation of mechanosensitive transcriptional pathway MRTF-SRF predominantly taking place in mesangial cells. Importantly, activation of MRTF-SRF transcriptional pathway was also identified in DN glomeruli in independent patient cohort datasets. Furthermore, ex vivo kidney perfusion suggested that the regulation of MRTF-SRF is a common mechanism in response to glomerular hyperfiltration.<h4>Conclusions</h4>Overall, our study presents a comprehensive single-cell transcriptomic landscape of early DN, highlighting mechanosensitive signaling pathways as novel targets of diabetic glomerulopathy."],"journal":["Genome medicine"],"pubmed_title":["Single-cell transcriptomics reveals a mechanosensitive injury signaling pathway in early diabetic nephropathy."],"pmcid":["PMC9830686"],"funding_grant_id":["616891","P30 DK020572","P30 DK081943"],"pubmed_authors":["Lindenmeyer MT","Liao Z","Cohen CD","Huber TB","Fermin D","Wiech T","Nelson RG","Krebs CF","Zielinski S","Gies SE","Liu S","Wu G","Schaper M","Delic D","Zhao Y","Aypek H","Bonn S","Nair V","Zhang T","Meyer-Schwesinger C","Grahammer F","Kretzler M","Lu S","Czogalla J"],"additional_accession":[]},"is_claimable":false,"name":"Single-cell transcriptomics reveals a mechanosensitive injury signaling pathway in early diabetic nephropathy.","description":"<h4>Background</h4>Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and histopathologic glomerular lesions are among the earliest structural alterations of DN. However, the signaling pathways that initiate these glomerular alterations are incompletely understood.<h4>Methods</h4>To delineate the cellular and molecular basis for DN initiation, we performed single-cell and bulk RNA sequencing of renal cells from type 2 diabetes mice (BTBR ob/ob) at the early stage of DN.<h4>Results</h4>Analysis of differentially expressed genes revealed glucose-independent responses in glomerular cell types. The gene regulatory network upstream of glomerular cell programs suggested the activation of mechanosensitive transcriptional pathway MRTF-SRF predominantly taking place in mesangial cells. Importantly, activation of MRTF-SRF transcriptional pathway was also identified in DN glomeruli in independent patient cohort datasets. Furthermore, ex vivo kidney perfusion suggested that the regulation of MRTF-SRF is a common mechanism in response to glomerular hyperfiltration.<h4>Conclusions</h4>Overall, our study presents a comprehensive single-cell transcriptomic landscape of early DN, highlighting mechanosensitive signaling pathways as novel targets of diabetic glomerulopathy.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2024-11-14T12:05:48.796Z","creation":"2024-11-14T12:05:48.796Z"},"accession":"S-EPMC9830686","cross_references":{"pubmed":["36627643"],"doi":["10.1186/s13073-022-01145-4"]}}