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Integrating single-cell RNA sequencing with spatial transcriptomics reveals immune landscape for interstitial cystitis [Supported by CapitalBio Technology]

Journal: Signal Transduction and Targeted Therapy   IF: 38.1027

Background

Interstitial cystitis/bladder pain syndrome (IC/BPS) is currently the most difficult disease in the field of gynecology and urology. The main clinical manifestations are frequent urination and severe pain in the overflow bladder. The disease has existed for more than 100 years, but the etiology is still unknown, what role immunity plays in the development of IC, and at which stage of the IC process it exerts its effector effect.

Method

Conclusions

1.IC Bladder Immunogram

A total of 135,091 CD45+ immune cells were captured from the bladders of IC patients and controls for identification and grouping and construction of IC immune profiles. Re-clustering analysis of T cells revealed that CD8+ T cells in the IC group had impaired efficacious function and reduced pathogen clearance ability. B cell re-clustering analysis revealed a strong humoral immune response in the IC bladder, and IgE can be used as a potential rapid diagnostic marker for IC.

Figure 1. Workflow and IC Bladder Immunogram

2.Clustering and grouping with spatial transcriptomics

The IC and control bladder were taken for spatial transcriptomics, cluster analysis and group identification, and were divided into 8 clusters in total.

Figure 2. IC and Control Bladder Spatial Transcriptome Atlas

3.MIA analysis of spatial transcriptomics and scRNA-seq reveals differential distribution of immune cells in IC versus control bladder

Gene characterization by spatial transcriptomic studies found that fibrosis-associated genes were highly expressed in different cell types in the IC group, again suggesting the possibility of severe fibrosis in the patient's bladder. Using MIA combined with single-cell data and spatial data, it was found that almost all immune subsets in IC bladder were enriched in the urothelial area or near fibroblasts, and the results again confirmed the importance of urothelial cells and fibroblasts in the pathogenesis of IC effect.

Figure 3. Differential distribution of immune subgroups in IC and control bladders after combining single-cell and spatial data

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