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Abstract: FR-PO682

Single-Cell Spatial Profiling of Glomerular Structures in Alport Syndrome

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Perin, Laura, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Sorg, Kristina, NanoString Technologies Inc, Seattle, Washington, United States
  • Zuckerman, Jonathan E., University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States
  • Sedrakyan, Sargis, Children's Hospital Los Angeles, Los Angeles, California, United States
Background

Many transcriptomics studies have described the molecular mechanisms underlying the progression of glomerular diseases, but very little is known about the gene spatial map of the different cell types, the heterogenous tissue niche composition, and how each glomerulus is affected during progressive CKD. Here we report the spatial characterization of gene expression at the single-cell level in renal biopsies of Alport Syndrome (AS) patients and from healthy subjects.

Methods

Using the Nanostring CosMX Spatial Molecular Imager (SMI) platform, and the human 1000-plex RNA panel we generated spatial maps of gene expression of kidney biopsies from AS patients (n=3) vs healthy subjects. Using H&E images we selected 29 fields of view (FOV) with dimensions of 0.9mm x 0.7mm for analysis. After data QC and normalization steps, we supervised cell typing. Spatial data analysis was achieved using different software and integrated with histopathology.

Results

We identified 36 clusters corresponding to different renal cells including glomerular, tubular, interstitial, and immune cell types. A spatial map of cell types in each FOV was reconstructed. Localization of podocytes, glomerular endothelial cells, and mesangial cells could be visualized. Color-coded gene expression maps of each cell type could be visualized at a single-cell resolution. Our analysis indicated the cellular composition varied between the different AS biopsies, revealing the presence of different cell types in the AS glomerulus not previously described including 3 different types of fibroblasts. We could also identify specific “glomerular immune niches.”

Conclusion

CosMx SMI analysis revealed significant differences in gene expression between AS and healthy biopsies at a single-cell level. These preliminary data using this technology may allow the discovery of potential new therapeutic targets for patients with AS, and other CKDs.