Abstract: FR-PO0302
Integrated scRNA-seq and Bulk RNA-seq Uncovering Metabolic Reprogramming and Potential Therapeutic Target in Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 1
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Shao, Fengmin, Henan Provincial People's Hospital, Zhengzhou, Henan, China
- Gu, Yue, Henan Provincial People's Hospital, Zhengzhou, Henan, China
- Liu, Ziyang, Henan Provincial People's Hospital, Zhengzhou, Henan, China
Background
Diabetic kidney disease (DKD) involves cell-type-specific metabolic dysregulation and intercellular crosstalk, but its mechanisms remain unclear. This study integrates scRNA-seq and bulk RNA-seq to analyze metabolic reprogramming in renal and immune cells, aiming to identify new DKD therapeutic targets.
Methods
ScRNA-seq datasets (GSE131882, GSE211785) were analyzed via Seurat for cell clustering, metabolic gene enrichment (scMetabolism, AUCell), and immune subtyping. Bulk RNA-seq (GSE142025, GSE199838) identified differentially expressed genes (limma), integrated with scRNA-seq to define shared metabolic pathways. Drug-gene interactions were screened via DGIdb, validated in DKD mice (histopathology) and high-glucose-treated podocytes (functional assays). Unsupervised NMF clustering classified DKD metabolic subtypes.
Results
ScRNA-seq revealed 18 cell clusters, with 28,296 metabolically active cells enriched in proximal tubule cells, macrophages, and podocytes, linked to dysregulated glycolysis, fatty acid oxidation, and immune signaling. Nine hub genes were identified: NR4A1 (epithelial development), adhesion genes (NDNF, NTNG1, PTPRO), and immune-related genes (PIK3R5, LCP2, PRKCB, PTPRC, RUNX1). Three metabolic subtypes were defined: cluster 1(cell adhesion/fibrosis), cluster 2 (protein metabolism/RNA regulation), cluster 3 (apoptosis/angiogenesis). Mechanistic validation showed that allopurinol, targeting the podocyte adhesion gene NTNG1, can ameliorate metabolic disorders in high-glucose-exposed podocytes.
Conclusion
This study reveals single-cell metabolic heterogeneity in DKD, identifies NTNG1-mediated podocyte dysfunction as a therapeutic target and allopurinol’s metabolic modulation potential. Defining three metabolic subtypes provides a basis for precision medicine in DKD.