Abstract: FR-PO169
Co-Registered Spatial Proteomics and Transcriptomics Identifies Scattered Proximal Tubule Cells
Session Information
- AKI: Mechanisms - II
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Eadon, Michael T., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Melo ferreira, Ricardo, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Winfree, Seth, University of Nebraska System, Lincoln, Nebraska, United States
- Lake, Blue, University of California San Diego, La Jolla, California, 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
- Parikh, Samir V., The Ohio State University College of Medicine, Columbus, Ohio, United States
- Barwinska, Daria, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Ferkowicz, Michael J., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Sabo, Angela R., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Gisch, Debora L., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Sutton, Timothy A., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Dunn, Ken, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Asghari, Mahla, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Rovin, Brad H., The Ohio State University College of Medicine, Columbus, Ohio, United States
- Kelly, Katherine J., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Jain, Sanjay, Washington University in St Louis, St Louis, Missouri, 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
Group or Team Name
- Kidney Precision Medicine Project
Background
THY1 (CD90) is a marker of mesenchymal stem cells. THY1 is expressed in the kidney and postulated to be upregulated in regenerative scattered tubular cells (STCs) of the proximal tubule (PT). The merged KPMP/HubMAP snRNAseq atlas does not contain a specific STC cluster. Using co-registered spatial transcriptomics (ST) and CO-Detection by indEXing (CODEX) immunofluorescence, we identified this STC sub-cluster within the snRNAseq atlas.
Methods
On consecutive sections of human kidney tissue (10 µm thick, N=3), CODEX (44 antibodies including THY1 and megalin) and ST (>20,000 genes detected) were performed and co-registered to spatially align protein and gene expression. Protein expression of THY1 and megalin defined regions for downstream ST comparison. Using ST, THY1+ megalin+ regions were compared to THY1- megalin+ regions. Differentially expressed ST genes (DEGs) were used to define a novel subcluster in the snRNAseq atlas.
Results
A novel STC subcluster was defined within the snRNAseq atlas. DEGs of STCs included THY1, SLC16A9, and PDZK1IP1. STC enriched pathways included Rho GTPase cycle, RAC1, growth factor signal transduction, and cell adhesion related pathways, consistent with the expected functions of this regenerative cell. Using Seurat anchor methodology, the THY1+ sub-cluster, defined by snRNAseq, mapped back to regions of THY1 protein expression.
Conclusion
The integration of CODEX, ST, and snRNAseq datasets facilitated the identification of an important PT cell type which was under-represented in the KPMP snRNAseq atlas.
Funding
- NIDDK Support