The single-cell transcriptomic landscape of early human diabetic nephropathy.
Parker C Wilson, Haojia Wu, Yuhei Kirita, Kohei Uchimura, Nicolas Ledru, Helmut G Rennke, Paul A Welling, Sushrut S Waikar, Benjamin D Humphreys
Author Information
- Parker C Wilson: Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO 63110.
- Haojia Wu: Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
- Yuhei Kirita: Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
- Kohei Uchimura: Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
- Nicolas Ledru: Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110.
- Helmut G Rennke: Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
- Paul A Welling: Department of Physiology, University of Maryland Medical School, Baltimore, MD 21201.
- Sushrut S Waikar: Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA 02115.
- Benjamin D Humphreys: Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110; humphreysbd@wustl.edu. ORCID
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, , mineralocorticoid receptor, and 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.
Aged
Calcium
Diabetes Mellitus
Diabetic Nephropathies
Female
Gene Expression Profiling
Humans
Kidney
Kidney Glomerulus
Kidney Tubules, Distal
Kidney Tubules, Proximal
Magnesium
Male
Middle Aged
Potassium
Sequence Analysis, RNA
Single-Cell Analysis
Transcriptome
Magnesium
Potassium
Calcium
