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Integrating single-cell RNA sequencing with spatial transcriptomics reveals immune landscape for interstitial
Liao Peng1, Xi Jin1, Bo-Ya Li1
1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.
Signal Transduction and Targeted Therapy
|May 19, 2022
Summary
Interstitial cystitis (IC) involves altered immune cell populations in the bladder, with increased T cells and neutrophils. Human polyomavirus-2 was detected in 95% of IC patients, suggesting a potential viral link.
Area of Science:
- Immunology
- Urology
- Genomics
Background:
- Interstitial cystitis (IC) is a chronic bladder condition with unknown causes, complicating diagnosis and treatment.
- Understanding the immune system's role in IC is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the immune cell landscape in the bladders of patients with interstitial cystitis (IC).
- To identify specific immune cell subpopulations and their spatial distribution in IC bladders compared to controls.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was performed on 135,091 immune cells from 15 female IC patients and 9 controls.
- Immune cell subpopulations were identified and their communication networks analyzed.
- Spatial transcriptomics was integrated with scRNA-seq data.
- Human polyomavirus-2 detection in urine samples.
Main Results:
- 22 immune subpopulations were identified, with M2-like macrophages, inflammatory CD14+ macrophages, and dendritic cells showing significant communication.
- IC bladders exhibited increased central memory CD4+ T cells, regulatory T cells, GZMK+CD8+ T cells, activated B cells, un-switched memory B cells, and neutrophils.
- Decreased CD8+ effector T cells, Th17 cells, follicular helper T cells, switched memory B cells, transitional B cells, and macrophages were observed in IC.
- A virus-related response was indicated, and human polyomavirus-2 was detected in 95% of IC patients' urine.
- Immune cells in IC bladders were enriched in the urothelial region or near fibroblasts, unlike control bladders where they were near urothelium and smooth muscle.
Conclusions:
- The study reveals a distinct immune landscape in IC bladders, characterized by specific immune cell alterations.
- Findings suggest a potential role for viral infections, specifically human polyomavirus-2, in IC pathophysiology.
- The altered spatial distribution of immune cells in IC bladders provides new insights into disease mechanisms.
