Abstract: SA-PO0312
Single-Nucleus and Spatial Transcriptomic Atlas of the Human Loop of Henle Reveals Novel Injury-Associated Cell States in Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 2
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Abedini, Amin, University of Maryland Medical Center Midtown Campus, Baltimore, Maryland, United States
- Kloetzer, Konstantin A., Medizinische Universitat Graz, Graz, Styria, Austria
- Susztak, Katalin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Background
Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease worldwide. While glomerular and proximal tubular injury in DKD has been extensively studied, the loop of Henle (LOH) has remained under-characterized. Given its physiological importance, defining LOH-specific injury responses in human DKD is critical to understanding disease progression.
Methods
We generated a single-nucleus RNA sequencing (snRNA-seq) atlas of the human LOH by integrating data from 65 kidney samples, including DKD and control specimens, profiling 35,156 nuclei. Integration was performed using the deep generative model scVI. Spatial transcriptomics was used to validate anatomical localization. Trajectory analysis was applied to uncover differentiation dynamics and injury transitions. Cross-species validation was performed using a publicly available DKD mouse atlas.
Results
We identified 11 distinct LOH-associated clusters, including classical segment-specific populations and three previously uncharacterized injury-associated cell states of LOH enriched in DKD: VCAM1+, HAVCR1+, and WFDC2+. These populations demonstrated unique transcriptional programs and were localized to specific regions of the nephron. Trajectory analysis revealed these injury-associated clusters as terminal endpoints along differentiation trajectories. Cross-validation with the DKD mouse atlas confirmed the presence of analogous injured LOH populations.
Conclusion
Our study provides an integrated snRNA-seq and spatial transcriptomic atlas of the human LOH in DKD. The identification of novel injury-associated cell states and their spatial and transcriptional contexts advances our understanding of tubular injury and highlights new avenues for therapeutic targeting in DKD.