| Authors |
Wilson PC, Wu H, Kirita Y, Uchimura K, Ledru N, Rennke HG, Welling PA, Waikar
SS, Humphreys BD
|
| Submitted By |
Benjamin Humphreys on 11/17/2020 |
| Status |
Published |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Year |
2019 |
| Date Published |
9/1/2019 |
| Volume : Pages |
116 : 19619 - 19625 |
| PubMed Reference |
|
| Abstract |
Diabetic 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.
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