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dc.contributor.authorWilson, P.C.
dc.contributor.authorWu, H.
dc.contributor.authorWelling, P.A.
dc.date.accessioned2019-10-03T14:14:46Z
dc.date.available2019-10-03T14:14:46Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85072630804&doi=10.1073%2fpnas.1908706116&partnerID=40&md5=a6173f7dde69e79586e3fcab5a50803e
dc.identifier.urihttp://hdl.handle.net/10713/11044
dc.description.abstractDiabetic nephropathy is characterized by damage to both the glomerulus and tubulointerstitium, but relatively little is known about accompanying cell-specific changes in gene expression. We performed unbiased single-nucleus RNA sequencing (snRNA-seq) on cryopreserved human diabetic kidney samples to generate 23,980 single-nucleus transcriptomes from 3 control and 3 early diabetic nephropathy samples. All major cell types of the kidney were represented in the final dataset. Side-by-side comparison demonstrated cell-type-specific changes in gene expression that are important for ion transport, angiogenesis, and immune cell activation. In particular, we show that the diabetic thick ascending limb, late distal convoluted tubule, and principal cells all adopt a gene expression signature consistent with increased potassium secretion, including alterations in Na+/K+-ATPase, WNK1, mineralocorticoid receptor, and NEDD4L expression, as well as decreased paracellular calcium and magnesium reabsorption. We also identify strong angiogenic signatures in glomerular cell types, proximal convoluted tubule, distal convoluted tubule, and principal cells. Taken together, these results suggest that increased potassium secretion and angiogenic signaling represent early kidney responses in human diabetic nephropathy.en_US
dc.description.urihttps://doi.org/10.1073/pnas.1908706116en_US
dc.language.isoen-USen_US
dc.publisherNational Academy of Sciencesen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.subjectDiabetic nephropathyen_US
dc.subjectRNA-seqen_US
dc.subjectSingle cellen_US
dc.titleThe single-cell transcriptomic landscape of early human diabetic nephropathyen_US
dc.typeArticleen_US
dc.identifier.doi10.1073/pnas.1908706116
dc.identifier.pmid31506348


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