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

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

PROVIDER: PRJNA1148155 | ENA |

REPOSITORIES: ENA

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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

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

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

| PRJNA1144887 | ENA

CHDR2007 Vulvar Premalignancies

Project description:The vulvar microbiome in lichen sclerosus and high-grade intraepithelial lesions

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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

Project description:Skin and vaginal microbiomes in vulvar lichen sclerosus

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

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

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Bacterial microbiome associated with lichen sclerosus

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Project description:vulvar skin microbiota 16S rRNA sequencing in healthy women and patients with vulvar lichen sclerosus

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microRNA expression in vulvar melanoma

Project description:microRNA expression in RNA isolated from formalin fixed, paraffin embedded tissue from vulvar melanoma compared to primary cutaneous melanoma

2022-07-16 | GSE208174 | GEO

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