Integrating single-cell RNA sequencing with spatial transcriptomics reveals immune landscape for interstitial cystitis

Liao, Peng; Jin, Xi; Li, Boya; Zeng, Xiao; Liao, Banghua; Jin, Tao; Chen, Jiawei; Gao, Xiaoshuai; Wang, Wei; He, Quanguo; Chen, Guo; Gong, Ling; Shen, Hong; Wang, Kun‐Jie; Li, Hong; Luo, Deyi

doi:10.1038/s41392-022-00962-8

Cited by 32 publications

(29 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, B cell SCs from the epidermis and dermis presented similar features. We found high expression of ISGs in epidermal B_SC3 and dermal B_SC4 and B_SC5, which were identified as plasma cells by the gene expression of CD38 , IGHG4 , and IGHG1 42 (Fig. 6 c, d, h, i and Supplementary Data 10 ).…”

Section: Resultsmentioning

confidence: 86%

Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus

Zheng

Mei

et al. 2022

Nat Commun

View full text Add to dashboard Cite

Discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE) are both types of lupus, yet the characteristics, and differences between them are not fully understood. Here we show single-cell RNA sequencing data of cutaneous lesions from DLE and SLE patients and skin tissues from healthy controls (HCs). We find significantly higher proportions of T cells, B cells and NK cells in DLE than in SLE. Expanded CCL20+ keratinocyte, CXCL1+ fibroblast, ISGhiCD4/CD8 T cell, ISGhi plasma cell, pDC, and NK subclusters are identified in DLE and SLE compared to HC. In addition, we observe higher cell communication scores between cell types such as fibroblasts and macrophage/dendritic cells in cutaneous lesions of DLE and SLE compared to HC. In summary, we clarify the heterogeneous characteristics in cutaneous lesions between DLE and SLE, and discover some specific cell subtypes and ligand-receptor pairs that indicate possible therapeutic targets of lupus erythematosus.

show abstract

Section: Resultsmentioning

confidence: 86%

Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus

Zheng

Mei

et al. 2022

Nat Commun

View full text Add to dashboard Cite

show abstract

“…Furthermore, CR2 is often present on B cells, follicular dendritic cells, and a fraction of T cells, which may affect B cell activity on many levels [36,37], thereby modulating the immunological response to IC/BPS. Peng et al [6] have established that the immunological milieu of IC/BPS encompasses diverse innate and adaptive immune cells. This adds to the growing body of evidence suggesting that inflammation and immunity play a significant role in the evolution of IC/BPS.…”

Section: Discussionmentioning

confidence: 99%

“…Peng et al [ 6 ] have established that the immunological milieu of IC/BPS encompasses diverse innate and adaptive immune cells. This adds to the growing body of evidence suggesting that inflammation and immunity play a significant role in the evolution of IC/BPS.…”

Section: Discussionmentioning

confidence: 99%

“…Although there is yet no adequate evidence to indicate that IC is an autoimmune illness, the aberrant immunological state of IC has been clearly documented in various research [11][12][13]. Previous bioinformatics studies using single-cell RNA sequencing found that local adaptive immune responses are a hallmark of IC [6], and Gamper et al [14] reported that immune-related pathways and immune cell infiltration were involved in the initiation and progression of IC/BPS, highlighting the pivotal role of immune mechanisms in the disease. Therefore, in this study, we integrated three different machine learning algorithms, including LASSO, SVM-RFE, and RF, to identify immune-related IC/BPS characteristic genes that might aid in the assessment of immune state in IC/BPS patients and facilitate their diagnosis.…”

Section: Introductionmentioning

confidence: 99%

“…Because oral medicines for IC/BPS are often ineffectual, the major goal of current treatment is to reduce the severity of the condition's symptoms [ 5 ]. Approximately 10% of IC/BPS complicated cases need invasive surgical therapy, such as improved bladder capacity through ileal cystoplasty and urinary bladder diversion surgeries [ 6 , 7 ], which certainly increases the physical and emotional impact on patients. Therefore, the development of novel molecular biomarkers for IC/BPS diagnosis and therapy is urgently required.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of Immune-Related Genes and Small-Molecule Drugs in Interstitial Cystitis/Bladder Pain Syndrome Based on the Integrative Machine Learning Algorithms and Molecular Docking

Jiang

Xinqing

Al-Danakh

et al. 2022

Journal of Immunology Research

View full text Add to dashboard Cite

Background. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, severely distressing clinical syndrome characterized by bladder pain and pressure perceptions. The origin and pathophysiology of IC/BPS are currently unclear, making it difficult to diagnose and formulate successful treatments. Our study is aimed at investigating the role of immune-related genes in the diagnosis, progression, and therapy of IC/BPS. Method. The gene expression datasets GSE11783, GSE11839, GSE28242, and GSE57560 were retrieved from the GEO database for further analysis. Immune-related IC/BPS differentially expressed genes (DEGs) were identified by limma. Three distinct machine learning approaches, least absolute shrinkage and selection operator (LASSO), support vector machine–recursive feature elimination (SVM-RFE), and random forest (RF), were used to find the immune-related IC characteristic genes. Nomogram and receiving operator curves (ROC) were plotted to measure characteristic effectiveness. Using the CMap database and the molecular docking approach, potential small-molecule medicines were found and verified. Consensus cluster analysis was also performed to separate the IC/BPS samples into immunological subtypes. Results. A total of 24 immune-related IC/BPS-DEGs were identified. When compared to the normal control group, the IC/BPS cohort had significantly more immune cell infiltration. Integrative machine learning methods discovered 5 IC/BPS characteristic genes (RASGRP1, PPBP, RBP4, CR2, and PROS2) that may predict IC/BPS diagnosis and immune cell infiltration. Furthermore, two immunological subgroups with substantial variations in immune cell infiltration across IC/BPS samples were identified, which were named cluster1 and cluster2, with the hallmark genes having greater expression in cluster2. Finally, bumetanide was shown to have the potential to be a medication for the treatment of IC/BPS, and it performed well in terms of its molecular binding with RASGRP1. Conclusion. We found and validated 5 immune-related IC/BPS genes (RASGRP1, PPBP, RBP4, CR2, and PROS2) and 2 IC/BPS immune subtypes. In addition, bumetanide was discovered to be a potential drug for treating IC/BPS, which may provide new insight into the diagnosis and immune therapy of IC/BPS patients.

show abstract

Intravesical Interferon Therapy vs Hyaluronic Acid for Pain Among Female Individuals With Interstitial Cystitis

Shen,

Peng,

Zeng

et al. 2024

JAMA Netw Open

Self Cite

View full text Add to dashboard Cite

ImportanceInterstitial cystitis (IC) is a debilitating condition. Although viral infection is a potential etiological cause, few studies have detected the effect of antiviral treatment.ObjectiveTo determine the efficacy and safety of intravesical interferon instillation compared with hyaluronic acid in female patients with IC.Design, Setting, and ParticipantsThis double-masked, randomized phase 2/3 clinical trial with parallel group design was implemented from October 2022 to April 2023 and had a 6-month follow-up period. The study was conducted at a single center. Eligible participants were female patients aged 18 to 70 years with a diagnosis of IC for more than 6 months. The last visit took place in October 2023. Data were analyzed between October and November 2023.InterventionPatients were randomized 1:1 to receive either intravesical instillation of interferon or hyaluronic acid.Main Outcomes and MeasuresThe primary end point was change in visual analog scale pain score. Secondary end points included changes in voiding frequency, functional bladder capacity, symptom index, and global response assessment. Adverse events were closely monitored.ResultsAmong the 52 patients, the mean (SD) age was 50.0 (14.1) years and they were randomized to either the interferon group (26 [50%]) or hyaluronic acid (26 [50%]). The visual analog pain score showed the interferon group decreased more significantly than hyaluronic acid (−1.3; 95% CI, −2.3 to −0.3; P = .02) at month 6, with 20 patients (77%) exhibiting a 30% or higher reduction in pain compared with baseline. Secondary end points of voiding frequency, functional bladder capacity, and nocturia episodes showed no significant difference between 2 therapies. However, interferon showed a significantly higher reduction in the Interstitial Cystitis Symptom Index (−3.0; 95% CI, −5.3 to −0.7; P = .01) and the Problem Index (−2.5; 95% CI, −4.5 to −0.4; P = .02) at month 6, with 22 patients (85%) presenting as moderately or markedly improved. The frequencies of adverse events were similar between 2 groups. Only 1 patient discontinued hyaluronic acid because of poor effectiveness.Conclusions and RelevanceIn this randomized clinical trial, female patients with IC could benefit from intravesical interferon therapy, without serious adverse events. These results offered hope for antiviral approaches in IC, but larger-scale, multicenter trials and long-term follow-up should be considered.Trial RegistrationClinicalTrials.gov Identifier: NCT05912946

show abstract

Integrating single-cell RNA sequencing with spatial transcriptomics reveals immune landscape for interstitial cystitis

Cited by 32 publications

References 53 publications

Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus

Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus

Identification of Immune-Related Genes and Small-Molecule Drugs in Interstitial Cystitis/Bladder Pain Syndrome Based on the Integrative Machine Learning Algorithms and Molecular Docking

Intravesical Interferon Therapy vs Hyaluronic Acid for Pain Among Female Individuals With Interstitial Cystitis

Contact Info

Product

Resources

About