Multi-omics analysis unveiled fibroblast-mediated pathogenesis in male genital lichen sclerosus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1230131 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Male genital lichen sclerosus (MGLSc), a chronic inflammatory dermatological condition, has been recognized for its profound implications on the quality of life among males. The exact etiological factors behind this prevalent condition remained largely enigmatic. In this research, we employed a multi-omics strategy to identify and elucidate the underlying histological biomarkers and the fundamental pathogenesis associated with MGLSc. Generally, a comprehensive cell atlas of MGLSc disease was constructed, highlighting a pronounced increase in T cells coupled with a remarkable reduction in keratinocytes within the MGLSc samples. Further insights elucidated the enhanced crosstalk between fibroblasts and T cells via the collagen-CD44 axis, and between fibroblasts and keratinocytes through the APP-CD74 signaling pathway. This molecular dialogue was implicated in the immune infiltration and hyperkeratosis observed in the dermal-epidermal layer of MGLSc. Subsequently, we integrated single-cell RNA sequencing data with genome-wide association study findings to explore the cell type-specific genes predisposing to the development of MGLSc. The analysis underscored the pivotal role of GAS1, which was enriched in fibroblasts and implicated in the pathogenesis of MGLSc progression. Collectively, we highlighted the critical role of fibroblasts in initiating MGLSc onset, generating interactions with T cells and keratinocytes, and eliciting the classical histological features of MGLSc.
2025-08-06 | GSE290798 | GEO
Project description:Comparing gene expression in Oral and genital lichen planus with normal oral and genital epithelium trying to idenitfy differently expressed genes in lichen planus compared to normal epithelium Total RNA obtained from oral and genital lichen planus epithelium compared with normal oral and genital epithelium
2013-11-08 | E-GEOD-52130 | biostudies-arrayexpress
Project description:Comparing gene expression in Oral and genital lichen planus with normal oral and genital epithelium trying to idenitfy differently expressed genes in lichen planus compared to normal epithelium
2013-11-08 | GSE52130 | GEO
Project description:Bacterial microbiome associated with lichen sclerosus Targeted loci
| PRJNA647685 | ENA
Project description:Vulvar diseases are a critical but often overlooked issue in women's health, impacting many women and frequently causing long-term physical and emotional challenges. Lichen sclerosus (LS) is a chronic inflammatory skin disease that causes scarring of the vulva and is associated with an increased risk of malignancy. The molecular pathogenesis of vulvar LS (VLS) is not well understood, preventing development of any FDA-approved therapies. Here, we utilize single-cell and spatial transcriptomics to analyze lesional and non-lesional skin from VLS patients, as well as healthy control vulvar skin. Our studies, which reveal histologic, cellular, and molecular heterogeneities within VLS, also identify unifying molecular changes across fibroblasts, immune cells, keratinocytes, and melanocytes in lesional skin. The findings depict a scenario of cellular stress and damage affecting both fibroblasts and keratinocytes, along with a complex immune landscape indicating enhanced CD8+ T cell cytotoxicity but also signs of exhaustion. They further suggest aberrant cell-cell signaling across, and increased activation of IFN, JAK/STAT and p53 pathways in, specific cell types. Using monolayer and organotypic culture models, we demonstrate that the depletion of select genes, which are downregulated in VLS lesional skin keratinocytes, partially recapitulates VLS-like stress-associated changes. Collectively, these data provide novel insights into the pathogenesis of VLS, identifying potential biomarkers and therapeutic targets for future research.
2025-01-27 | GSE274068 | GEO
Project description:Vulvar diseases are a critical but often overlooked issue in women's health, impacting many women and frequently causing long-term physical and emotional challenges. Lichen sclerosus (LS) is a chronic inflammatory skin disease that causes scarring of the vulva and is associated with an increased risk of malignancy. The molecular pathogenesis of vulvar LS (VLS) is not well understood, preventing development of any FDA-approved therapies. Here, we utilize single-cell and spatial transcriptomics to analyze lesional and non-lesional skin from VLS patients, as well as healthy control vulvar skin. Our studies, which reveal histologic, cellular, and molecular heterogeneities within VLS, also identify unifying molecular changes across fibroblasts, immune cells, keratinocytes, and melanocytes in lesional skin. The findings depict a scenario of cellular stress and damage affecting both fibroblasts and keratinocytes, along with a complex immune landscape indicating enhanced CD8+ T cell cytotoxicity but also signs of exhaustion. They further suggest aberrant cell-cell signaling across, and increased activation of IFN, JAK/STAT, and p53 pathways in specific cell types. Using monolayer and organotypic culture models, we demonstrate that the depletion of select genes, which are downregulated in VLS lesional skin keratinocytes, partially recapitulates VLS-like stress-associated changes. Collectively, these data provide novel insights into the pathogenesis of VLS, identifying potential biomarkers and therapeutic targets for future research.
2025-01-27 | GSE274837 | GEO
Project description:It seems established that genetic and epigenetic determinants drive the multifactorial pathogenic processes in vulvar lichen sclerosus (VLS). Aberrant expression of microRNAs (miRNAs) has been observed in a few studies suggesting potential involvement. We aimed to assess the expression of miRNAs both in VLS and in healthy keratinocytes and fibroblasts cultured separately. The differential analysis led to the identification of 171 and 111 microRNAs with an expression difference of at least 1.5-fold between VLS and healthy samples, in keratinocytes and fibroblasts, respectively. More than 80% of the 111 microRNAs identified as differentially expressed in fibroblasts were also found to be differentially expressed in keratinocytes. A number of dysregulated miRNAs are involved in inflammation and fibrotic processes, namely miR-10a-5p and 3p, miR-143-3p and 5p, miR-181a-5p and 3p, miR-181b-5p and 3p, miR-21-3p, miR-146b-5p and miR-29c. Our results showed a clear separation of VLS keratinocytes and fibroblasts from healthy cells in terms of miRNA expression. It is noteworthy that the most dysregulated miRNAs are implicated in inflammatory and fibrotic pathways. It is conceivable that miRNA expression is functional in regulating pathogenetic mechanisms of LS.
2023-12-13 | GSE249675 | GEO
Project description:Introduction:Lichen sclerosus (LS) is a chronic inflammatory disease affecting mainly the genital mucous membranes in both sexes. In the past, different terms were used to describe the disease, rendering a unique and specific clinical classification impossible. Aim:New therapeutic approaches are being defined, which may contribute to a proper clinical management, however, a stage classification is essential to better define appropriate treatment for every stage of the disease. Material and methods:One hundred and fifteen patients (50 women and 65 men) with a diagnosis of LS were enrolled between January 2014 and September 2016. All patients underwent cutaneous biopsy to confirm the clinical diagnosis of LS. Clinical and symptomatological parameters were used in order to put the patients into the correct stage of LS. The Dermatology Life Quality Index (DLQI) was used to classify patients based on subjective symptoms. Different cutaneous alterations and structural modifications of the genital mucosa were also taken into consideration in order to assign every patient to a specific stage. Conclusions:Lichen sclerosus is clinically described differently in females and in males and every form of LS is put into one of two stages according to the degree of severity: early and late stages. Within the clinical practice, it is useful to screen patients for groups of early or late forms of the disease in order to obtain a uniform subdivision of patients: those who may benefit from localized treatments, require a systemic drug and must undergo physical treatments (surgical, stem cells infiltrations).
| S-EPMC6232547 | biostudies-other
Project description:The diagnosis of genital lichen sclerosus (LS) is often confirmed by obtaining a skin biopsy, which can lead to unwanted complications and is uncomfortable in the sensitive genital area. Thus, there is a need of finding novel, non-invasive techniques that can rapidly and accurately diagnose LS. The present study investigated the potential for reflectance confocal microscopy (RCM) to diagnose LS compared with healthy penile skin and other common penile skin disorders in males. A total of 30 male patients, including patients with LS, nonspecific balanoposthitis, plasma cell balanitis and psoriasis, and healthy individuals were included and were subject to non-invasive RCM investigation. Prominent fiber-like structures, representing hyaline sclerosis, were observed in the RCM images for almost half of the patients. Differences between healthy penile skin and LS were confirmed by identifying the edged papillae on healthy skin and their absence or obscureness in patients with LS. Notably, RCM could detect the atypical honeycomb pattern referring to dysplasia in 1 patient with LS with penile intraepithelial neoplasia. In conclusion, the present study demonstrated that RCM can detect sclerosis in penile LS. RCM can potentially become a valuable tool for monitoring patients with LS for dysplasia providing a useful non-invasive diagnostic tool for genital disorders.
| S-EPMC9115641 | biostudies-literature
Project description:The Lobaria pulmonaria holobiont consists of algal, fungal, cyanobacterial, and integrated diverse bacterial components and thrives in undisturbed, humid forests. We set out to investigate the role of the microbiome of L. pulmonaria in the adaptation of this ecologically sensitive lichen species to diverse climatic conditions. Our central hypothesis posited that microbiome composition and functionality aligns with continental-scale climatic parameters related to temperature and precipitation. In addition, we tested whether short-term weather dynamics, sampling season, and the genotypes of the fungal and algal partners influenced the variation in the lichen microbiome. Insights into compositional and functional changes within the microbiome were obtained using metaproteomics. Comparative examinations between Sub-Atlantic Lowland (SAL) and Alpine (ALP) regions unveiled the distinct impact of climate on microbiome functions.
2024-07-03 | PXD049079 | Pride