Abstract: FR-PO0314
Single-Cell Molecular and Digital Pathology Characterization of Neovascularization 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
- Melo Ferreira, Ricardo, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Lucarelli, Nicholas, University of Florida, Gainesville, Florida, United States
- Cheng, Ying-Hua, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Phillips, Carrie L., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Gisch, Debora L., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Bowen, William S., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Dagher, Pierre C., Indiana University School of Medicine, Indianapolis, Indiana, United States
- El-Achkar, Tarek M., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Jain, Sanjay, Washington University in St Louis School of Medicine, St. Louis, Missouri, United States
- Rosenberg, Avi Z., Johns Hopkins Medicine, Baltimore, Maryland, United States
- Sarder, Pinaki, University of Florida, Gainesville, Florida, United States
- Eadon, Michael T., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background
Histopathologic features of diabetic kidney disease (DKD) may include nodular mesangial sclerosis, podocyte foot process effacement, and neovascularization. Molecular drivers underlying these features at the single-cell level are not fully understood. Given the expanding armamentarium of DKD therapies, companion diagnostics uniting digital pathology and spatial transcriptomics (ST) may aid in combinatorial therapy selection. We characterized the in situ molecular signature of every endothelial cell, mesangial cell, and podocyte within the histologic context in healthy and DKD glomeruli.
Methods
We selected healthy reference (Ref, N = 9) and DKD (N = 20) specimens for consecutive Xenium processing with digital histopathology analysis in 3 Ref and 4 DKD. We segmented and analyzed digital pathology for every recognizable cell within each glomerular profile and linked single cell pixel-level features to Xenium molecular signatures, defining cell identity and state (health, injury, repair). On another subset (3 Ref, 4 DKD), a sequential section was analyzed with Visium HD to estimate single cell transcription factor activity. ST cell type mapping was informed by the KPMP single nucleus atlas.
Results
Xenium showed that proliferative (pr) glomerular endothelial cells (ECs) were increased in DKD (Fishers, OR=1.2, p<2x10-16), while canonical glomerular ECs were decreased (OR 0.7, p<2x10-16). Visium HD identified a 2-fold increase in average MEF2C activity in DKD (t test, p<2x10-16). Digital histomorphology, such as cell shape, texture, and nuclear size were evaluated for association with EC phenotypes. We associated MEF2C activity with neovascularized glomeruli (Figure 1).
Conclusion
We identified increased prEC single cell abundance in glomeruli with neovascularization, also associated with MEF2C transcription factor activity and endothelial cell morphologic changes. MEF2C or its downstream targets may serve as future immunohistochemical markers of neo-vessels.
Funding
- NIDDK Support