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Abstract: TH-OR11

Unified Cross-Species Kidney Single-Cell Atlas: Unraveling Conserved Cellular Features and Species-Specific Adaptations

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms


  • Kloetzer, Konstantin A., University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Abedini, Amin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Balzer, Michael S., University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Liang, Xiujie, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Levinsohn, Jonathan, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Susztak, Katalin, University of Pennsylvania, Philadelphia, Pennsylvania, United States

The kidney plays a critical role in maintaining systemic homeostasis, yet our current understanding of species differences, health states, and changes in disease states remains limited. Owing to the kidney's complex cellular architecture, single-cell tools can provide pivotal insight into these processes.


We processed seven large renal single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics datasets derived from healthy and disease-affected mouse, rat, and human samples. Following meticulous quality controls, we harmonized gene symbols and integrated data using deep generative modeling (scVI). A variety of computational tools were utilized to comprehend cell type conservations as well as species and disease state-specific changes.


We present the first comprehensive, fully integrated interspecies renal snRNA-seq atlas, comprising more than 140 samples and over 1 million cells - the largest kidney cell atlas to date. Our atlas uncovers over 100 distinct cell states, providing a detailed understanding of conserved biological functions, marker genes, species-specific differences, and cellular adaptations in response to disease. Conserved cell types were anatomically positioned using spatial transcriptomics data. By employing the concept of Differentially Expressed Gene Ontology terms (DEGOs) – which focus on mean expression values for functional gene sets rather than individual genes – we highlighted the conserved renal physiology at the single-cell and spatial level. We observed notably fewer proximal tubule S3 segment cells in the human kidney compared to rodents. We identified a conserved injured proximal tubule subset with its unique markers. Additionally, we discovered novel cell types in the loop of Henle cluster expressing developmental process-related gene signatures.


This comprehensive kidney single-cell atlas serves as a valuable resource, offering a consistent reference across species with standardized cell terminology. It enables a deeper understanding of kidney biology and paves the way for developing novel therapeutic strategies.


  • NIDDK Support