ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: TH-OR74

Subpopulations of Injured Proximal Tubular Cells in Allograft Kidneys: Computational Analysis of Available scRNAseq Datasets

Session Information

Category: Transplantation

  • 2101 Transplantation: Basic

Authors

  • da Silva Fernandes, Sylvina, Universiteit Antwerpen, Antwerpen, Belgium
  • Boor, Peter, Universitatsklinikum Aachen, Aachen, Nordrhein-Westfalen, Germany
  • Vervaet, Benjamin Arthur, Universitatsklinikum Aachen, Aachen, Germany

Group or Team Name

  • Laboratory of Pathophysiology and Laboratory of Nephropathology.
Background

Single-cell RNAseq has been used to investigate the cellular phenotypical landscape of allograft kidneys undergoing ischemia/reperfusion injury. Rather less attention has been paid to the proximal tubular cell (PTC) population. Here, we re-analyzed human single-cell (sc)RNAseq datasets of histologically normal and injured allograft kidneys to characterize PTC phenotypes.

Methods

We analyzed five publicly available human scRNAseq datasets, including data on histologically normal appearing kidney allografts (two datasets) and allografts with acute tubular injury (three datasets). Using R software (Seurat, DESeq2, clusterProfiler), we identified “injured” and “healthy” PTC populations, and determined their differentially expressed genes (DEGs) and enriched pathways. We compared the DEGs and pathways of “injured PTC populations” from histologically normal allografts with those of adverse allografts.

Results

In all datasets, we identified at least one healthy and one injured PTC population. The injured PTCs were characterized by the expression of established PTC injury markers (CDH6, SPP1, IL32). Most of the commonly dysregulated pathways in the injured PTCs were related to energy metabolism: fatty acid/amino acid metabolism, oxidative phosphorylation, glycolysis/gluconeogenesis. The injured PTCs in one of the two histologically normal allograft datasets presented markers of failed repair (upregulated DCDC, downregulated SLC5A12/SLC7A13). These PTCs also showed enrichment of Wnt- and Hippo-signaling pathways, previously identified in a mouse model of AKI-to-CKD progression. Although the average relative proportion of injured PTCs was lower in the histologically normal allografts (4,6% +/- 4,6%) compared to the injured allografts (15,1% +/- 9,9%), inherent inter-dataset heterogeneity did not reveal statistical significance.

Conclusion

We identified and characterized common PTC subpopulations across five allograft scRNAseq datasets. We found that histologically normal appearing allograft kidneys contain an injured PTC population, which is shared with allografts with acute tubular injury.