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 and Benjamin D. Humphreys ()
Additional contact information
Parker C. Wilson: Washington University in St. Louis
Yoshiharu Muto: Washington University in St. Louis
Haojia Wu: Washington University in St. Louis
Anil Karihaloo: Novo Nordisk Research Center Seattle Inc
Sushrut S. Waikar: Boston University School of Medicine, Boston Medical Center
Benjamin D. Humphreys: Washington University in St. Louis

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-32972-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32972-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-32972-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().