Abstract: FR-PO267
Cell Type- and Diabetic Kidney Disease-Specific Expression of Long Noncoding RNAs in Human Kidneys
Session Information
- Diabetic Kidney Disease: Basic - 1
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- de Klerk, Juliette A., Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, Netherlands
- Slieker, Roderick, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
- Wu, Haojia, Department of Medicine, Division of Nephrology, Washington University School of Medicine, Saint Louis, Missouri, United States
- Muto, Yoshiharu, Department of Medicine, Division of Nephrology, Washington University School of Medicine, Saint Louis, Missouri, United States
- Herrewijnen, Floris, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
- 't Hart, Leen M., Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
- Postma, Rudmer J., Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands
- van der Pluijm, Loïs, Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands
- Peerlings, Janneke H D, Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, Netherlands
- Baelde, Hans J., Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands
- Gerrits, Tessa, Department of Pathology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands
- Van Zonneveld, Anton Jan, Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands
- Humphreys, Benjamin D., Department of Medicine, Division of Nephrology, Washington University School of Medicine, Saint Louis, Missouri, United States
- Bijkerk, Roel, Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands
Background
Long non-coding RNAs (lncRNAs) play diverse roles within cells, often show cell type-specific expression and impact kidney function. Despite the emergence of single-cell RNA sequencing studies to understand cell specificity, past studies focus solely on the protein coding genome. We hypothesize that lncRNAs, due to their cell type-specific nature, have crucial functions within specific renal cells. Our study aims to characterize and explore the roles of lncRNAs in different cell types in human kidneys and their relationship with diabetic kidney disease (DKD).
Methods
To focus specifically on the non-coding region of the genome We reprocessed single-cell RNA sequencing data from kidney samples that were obtained from six control patients, and seven patients with diabetic kidney disease. We characterized lncRNAs in individual cells and identified cell type-specific lncRNAs as well as lncRNAs which were differentially expressed in DKD. RNAscope was used to validate identified lncRNA expression in the kidney.
Results
Among the 10,342 lncRNAs present in the single-cell RNA-seq dataset (constituting 37.5% of the total transcripts in the scRNA-seq), 349 exhibit cell type-specific expression across 15 different cell types in the human kidney, with 104 showing significant associations with DKD. We set up gene regulatory networks to explore functional roles of differentially expressed lncRNAs in the different cell types. We identified TARID, a podocyte-specific lncRNA, to be upregulated in DKD, and to strongly correlate with genes involved in podocyte morphology abnormalities (such as abnormal podocyte foot processes), nephrotic syndrome, and albuminuria, while podocyte-specific expression of TARID was validated using RNAscope.
Conclusion
Our study provides a valuable resource for lncRNA expression across cell types in the human kidney and as illustrated by the identification of the podocyte specific lncRNA TARID, highlights the potential importance of cell type-specific lncRNAs in diabetic kidney disease.