Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression
Parker C. Wilson, Yoshiharu Muto, Haojia Wu, Anil Karihaloo, Sushrut S. Waikar, Benjamin D. Humphreys
Abstract
The proximal tubule is a key regulator of kidney function and glucose metabolism. Diabetic kidney disease leads to proximal tubule injury and changes in chromatin accessibility that modify the activity of transcription factors involved in glucose metabolism and inflammation. Here we use single nucleus RNA and ATAC sequencing to show that diabetic kidney disease leads to reduced accessibility of glucocorticoid receptor binding sites and an injury-associated expression signature in the proximal tubule. We hypothesize that chromatin accessibility is regulated by genetic background and closely-intertwined with metabolic memory, which pre-programs the proximal tubule to respond differently to external stimuli. Glucocorticoid excess has long been known to increase risk for type 2 diabetes, which raises the possibility that glucocorticoid receptor inhibition may mitigate the adverse metabolic effects of diabetic kidney disease.
Datasets
1. Human kidney cortex snRNA-seq data from donors with and without diabetic kidney disease
Metadata
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Source data
https://cellxgene.cziscience.com/collections/b3e2c6e3-9b05-4da9-8f42-da38a664b45b
Alias names
GSE195460, GSE151302, GSE131882, PMID36068241, PMC9448792
Cite this study
Wilson, P.C., Muto, Y., Wu, H., Karihaloo, A., Waikar, S.S. and Humphreys, B.D., 2022. Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression. Nature communications, 13(1), p.5253. https://doi.org/10.1038/s41467-022-32972-z
