Abstract: SA-PO0650
Single-Nucleus Transcriptomic Profiling of a Patient with ApoE2 Homozygote Glomerulopathy: Bridging Molecular and Histopathology Landscapes
Session Information
- Monogenic Kidney Diseases: Tubular and Other
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Zhu, Jiahao, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- Liu, Yan, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- Xu, Lubin, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- Huang, Zheng, Chinese Academy of Sciences Beijing Institute of Genomics, Beijing, China
- Jiang, Lan, Chinese Academy of Sciences Beijing Institute of Genomics, Beijing, China
- Chen, Limeng, Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
Background
ApoE2 homozygote glomerulopathy (ApoE2-GP) is a rare lipid metabolism disorder associated with ApoE2/2 genotype and type III hyperlipoproteinemia, characterized by extensive glomerular foam cell infiltration. While lipid accumulation in macrophages has been implicated in its pathogenesis, the molecular response of other renal cells remains poorly understood.
Methods
In a patient diagnosed with ApoE2-GP who underwent renal biopsy, we collected the clinical and pathological data, and performed snRNAseq of snap-frozen renal biopsy samples using the UDA-seq technology. Three time-zero transplant biopsy samples were used as healthy control.
Results
A 66-year-old male presenting with edema, proteinuria (4.59 g/24h), renal impairment (SCr 134 μmol/L), hypoalbuminemia (31 g/L), and hyperlipidemia. Renal biopsy revealed mesangial expansion with oil-red-O-positive foam cells in the capillary lumen and mesangial area (Fig. 1a). Electron microscopy found lipid vacuoles and inclusions in mesangial and endothelial cells (Fig. 1b). Whole-exome sequencing showed ApoE2/2 genotype, confirming the diagnosis of ApoE2-GP. Single-nucleus RNA-seq showed upregulation of lipid-related genes (e.g., ABCA1, PPARG) in macrophages and higher “foam cell differentiation” signature than control (Fig. 1e). Endothelial cells showed lipid metabolic dysregulation and stromal cells, including fibroblasts and vascular smooth muscle cells, exhibited pro-fibrotic activation. NicheNet identified disease-related intercellular crosstalk, such as ICAM1/ITGAM implicating macrophage-endothelial adhesion and podocyte - fibroblast IGF1-LAMC3 axis.
Conclusion
This is the first single cell RNA sequencing study of ApoE2-GP. Integrated analysis of transcriptomic and histopathological characteristics highlighted the role of not only macrophages, but also endothelial and stromal cells.
Figure 1. (a) and (b), pathological findings. (c-g), single cell analysis.