Abstract: FR-PO0323
Podocyte Heterogeneity in Diabetic Kidney Disease: Deciphering the Metabolic Subtype and Its Cross-Talk with Parietal Epithelial Cells
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
- Zhang, Li, Division of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
- Li, Jiaying, Division of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
- Li, Luan, Division of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
- Yang, Yan, Division of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
- Liang, Xinling, Division of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Background
Podocyte injury critically contributes to diabetic kidney disease (DKD) progression, yet the cellular heterogeneity of podocytes and their distinct contributions to disease progression remains poorly characterized.
Methods
Single-cell RNA sequencing (scRNA-seq) was performed on kidneys from db/db (n=4) and db/m (n=4) mice to identify podocyte subtypes. We analyzed their functional characteristics, key transcription factors, interactions with parietal epithelial cells (PECs), and clinical relevance.
Results
Podocyte heterogeneity was mapped through single-cell RNA sequencing analysis.We identified three distinct subtypes: Cryab+ metabolic subtype (Metab-subtype), Slc6a6+ transitional phenotype (Trans-subtype), Magi2+ adhesion subtype (Differentiated-subtype). Trajectory analysis indicated that both the Trans-subtype and Differentiated-subtype originated from the Metab-subtype. Transcription factor analysis suggested that Wt1 may play a key role in subpopulation conversion. Conjoint trajectory analysis of podocytes and PECs revealed impaired differentiation of Cryab+ PECs into Cryab+ podocytes in DKD. We further uncovered intercellular crosstalk between Cryab+ podocytes and PECs, predominantly mediated by the VEGFA-NRP2 and APP-SORL1 ligand-receptor pairs. Clinically, the Cryab+ subtype exhibited a negative correlation with proteinuria and serum creatinine but a positive correlation with eGFR, suggesting that its decline contributes to unfavorable prognosis of DKD .
Conclusion
These findings provide novel insights into podocyte heterogeneity and regeneration in DKD, highlighting potential therapeutic targets.
Single-Cell RNA Sequencing Reveals Podocyte Heterogeneity: Three Distinct Subtypes and Pseudotemporal Dynamics of Podocyte-PEC Interactions in Diabetic Nephropathy
Funding
- Government Support – Non-U.S.