Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-omics analysis unveiled fibroblast-mediated pathogenesis in male genital lichen sclerosus

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE290798 | GEO | 2025/08/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

MicroRNAs expression in vulvar lichen sclerosus keratinocytes and fibroblasts: further evidence and possible pathogenetic implications from an observational study

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

T-lymphocyte recruitment and retention in lichen planus

Project description:Lichen planus (LP) is a chronic, debilitating, inflammatory disease of the skin and mucous membranes that affects 1-2% of Americans. Its molecular pathogenesis remains poorly understood, and there are no FDA-approved treatments. We performed single cell RNA sequencing on blood and affected and unaffected skin from 7 LP patients. LP affected skin exhibited a robust immune infiltrate primarily composed of CD8 T-cells. These cells were specifically recruited by cytokines secreted by both superficial and dermal layers of skin. Basal keratinocytes and fibroblasts secrete CXCL9 and CXCL10, and fibroblasts secrete CCL19. Molecular analysis of LP skin and blood samples increased our understanding of disease pathogenesis and identified CCL19 as a new therapeutic target for treatment.

2024-10-03 | GSE254542 | GEO

Single cell profiling of lichen planus identifies type I interferon response and potential therapeutic targeting

Project description:Cutaneous lichen planus (LP) is an inflammatory skin disease characterized by an interface dermatitis with lymphocyte infiltration and keratinocyte cell-death. Previous studies suggest that LP inflammation is dominated by a type I immune response involving IFN-g but its pathogenesis remains not fully elucidated yet. To investigate the inflammatory mechanisms underlying LP, we performed single-cell RNA sequencing on LP compared with healthy control skins. We demonstrate that LP skin is imprinted by a type I interferon (IFN-I)-rich environment. While all immune cells are imbued with this interferon signature, we highlight unique subsets of inflammatory keratinocytes and fibroblasts highly influenced by IFN-I.

2025-04-02 | GSE243940 | GEO

Transcrpitomic analysis of Oral lichen planus with immumosuppressive therapy

Project description:We compared the transcriptomes of tissues from Oral lichen planus patients with immunosuppressive therapy to reveal the biological mechanism of oral lichen planus treatment.

2022-06-05 | GSE204663 | GEO

Type I interferons dominate cutaneous lichen planus inflammatory landscape driving the interface dermatitis reaction [NTERT]

Project description:Cutaneous lichen planus (LP) is a chronic inflammatory skin disease histologically characterized by an interface dermatitis with lymphocyte infiltration and keratinocyte cell-death. Previous studies suggest that LP inflammation is dominated by a type I immune response involving IFN-g but its pathogenesis remains not fully elucidated yet. To investigate the inflammatory mechanisms underlying LP, we performed single-cell RNA sequencing on LP compared with healthy control skins. We demonstrate that lesional skin from patient with LP is imprinted by a type I interferon (IFN-I)-rich environment, involving all the main skin cell components. While all immune cells are imbued with this interferon signature, we highlight unique subsets of inflammatory keratinocytes and fibroblasts highly influenced by IFN-I near the epidermis-dermis junction. We also show a unique CD8+CXCL13+ T cell population exhibiting cytotoxic and epidermis-homing markers together with an enrichment in inflammatory CD16+ myeloid cells in LP skin. Herein, we illustrate that IFN-I education on all major skin cell types and particularly in keratinocytes drives the interface dermatitis reaction, thus orchestrating the cross-talk between immune and stromal cells in LP skin. Last, we suggest the effectiveness of targeting the common IFN-I receptor, IFNAR1, to switch off the activation of inflammatory pathways in an ex-vivo model of LP skin and in on patient with lupus lichen skin lesions. Together, our data provide a comprehensive characterization of LP immunopathogenesis and demonstrate the strong involvement of IFN-I in its inflammatory landscape, providing arguments for the therapeutic use of drugs targeting IFN-I pathway in patients with LP.

2025-04-03 | GSE240461 | GEO

Single-cell and spatial transcriptomics of vulvar lichen sclerosus reveal multi- compartmental alterations in gene expression and signaling cross-talk

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

Single-cell and spatial transcriptomics of vulvar lichen sclerosus reveal multi-compartmental alterations in gene expression and signaling cross-talk

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

Gene expression profiling of oral and genital lichen planus epithelium and normal oral and genital epithelium

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

Profiling of Salivary Exosomal microRNAs in Oral Lichen Planus Patients [set 2]

Project description:In this study, we compared microRNA (miRNA) profiles of salivary exosomes of patients with oral lichen planus with those of healthy controls. Saliva samples from 16 patients with oral lichen planus and 8 healthy controls were divided into 2 sets and were examined by performing miRNA microarray analysis. Examination of 8 oral lichen planus patients and 4 healthy controls. Each patient and control represent pooled RNAs from salivary exosomes of 8 patients and 4 healthy controls, respectively. Please note that each set (i.e. set1 and set2) was analysed independently.

2015-04-30 | E-GEOD-68407 | biostudies-arrayexpress

Profiling of Salivary Exosomal microRNAs in Oral Lichen Planus Patients [set 1]

2015-04-30 | E-GEOD-68406 | biostudies-arrayexpress