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Dr. Parker C. Wilson, Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Wash-ington University in St. Louis, USA: "Single Cell Profiling in Diabetic Kidney Disease"
2021.04.26 |
| Date | Wed 02 Jun |
| Time | 15:00 — 16:00 |
| Location | Zoom ID No: 67623409102 |
Diabetic kidney disease (DKD) is characterized by increased glucose reabsorption and proximal tubule injury that leads to progressive renal dysfunction. We performed single nucleus RNA (snRNA-seq) and ATAC sequencing (snATAC-seq), in parallel, on human kidney cortex samples obtained from 5 healthy donors, 5 patients with early DKD and 3 patients with advanced DKD to evaluate cell-specific changes in type 2 diabetes. Side by side comparison showed cell-type-specific transcriptional changes that promote gluconeogenesis and ammoniagenesis. We observed increased expression of gluconeogenic genes PCK1, ALDOB, FBP1, and G6PC and the sodium bicarbonate exchanger, SLC4A4, in the diabetic proximal tubule (Figure 1; green=upregulated, red=downregulated). Transcriptional changes were associated with cell-type-specific differential chromatin accessibility in regulatory regions that were linked to their respective promoters via predicted chromatin interactions. Differentially accessible regions in the proximal tubule were enriched for NFkB binding motifs. Our analysis reveals that early diabetes induces changes in chromatin accessibility that promote gluconeogenesis and ammoniagenesis in the proximal tubule and suggests utility for single cell multi-omic analyses.
Zoom meeting: https://aarhusuniversity.zoom.us/j/67623409102
Host: Dr. Joanna Kalucka, Department of Biomedicine
On behalf of the organizer
Søren Brandt Poulsen
Administrative Research Theme Coordinator
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