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Abstract: SA-OR22

Single-Cell RNA Sequencing Provides Insights into the Mechanism Through Which Adaptive Immune Cells Promote Injury-Induced Cyst Formation

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic


  • Zimmerman, Kurt, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Yoder, Bradley K., The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Mrug, Michal, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Hopp, Katharina, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States

Inducible disruption of cilia related genes in adult mice results in slow progressing cystic disease, which can be greatly accelerated by renal injury. However, cells that promote accelerated cystogenesis following renal injury are poorly understood.


To identify cells that may be responsible for driving rapid, injury induced cystic disease, we performed single cell RNA sequencing on cells isolated from sham operated CAGGCreERT2+ Ift88f/f (hereafter referred to as cilia mutant mice), ischemia-reperfusion (IR) injured cre negative control, and IR injured cilia mutant mice 56 days post injury, a time point in which injured cilia mutant mice had mild cystic disease.


Comparison of single cell RNA sequencing data from sham- and injured- cilia mutant mice indicate that renal injury in the setting of cilia loss results in alterations in T cell clusters with limited differences in other cell populations. In contrast, single cell RNA sequencing data comparing injured cre negative control and injured cilia mutant mice reveals that loss of primary cilia in the setting of IR injury resulted in major changes in clusters of tubular epithelia and macrophages with minimal effects on T cells. These data suggest that accelerated cystogenesis in cilia mutant mice requires both injury induced changes in T cells as well as cilia-dependent alterations in the injured epithelium and macrophages. Using NicheNet to identify ligand-receptor-gene regulatory networks, we show that T cells from injured cilia mutant mice produce ligands that cause alterations in the gene expression signature of the cilia mutant epithelium and macrophages suggesting that these cells are master regulators of injury induced cystic disease. In agreement with this hypothesis, our data indicate that loss of adaptive immune cells (including T cells) significantly reduced injury induced cystic disease. In contrast, loss of adaptive immune cells did not affect cyst progression in the absence of injury in multiple cystic models, even when animals were aged out several months.


Collectively, our data indicate that IR injury creates a unique population of ligand-producing T cells that crosstalk with macrophages and epithelium of cilia mutant mice to drive rapid, injury induced cystogenesis.


  • NIDDK Support