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PROVIDER: PRJEB55817 | ENA |
REPOSITORIES: ENA
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Project description:Millions suffer from skin diseases. Functional epidermal stem cells are needed in skin therapy or drug screening in vitro. We obtained functional epidermal stem cells with intact stemness and cell junctions by treating them with wnt3a. Moreover, epidermal stem cell-derived exosomes were useful in epidermal development. Finally, functional epidermal 3D organoids with polarity were cultured using wnt3a and the supernatant derived from epidermal stem cells and fresh medium in a 1:1 ratio. These results provide novel directions for the improvement of skin organoids and their potential in clinical application.
2020-07-14 | PXD020351 |
Project description:This study focused on patients with estrogen receptor positive/human epidermal growth factor receptor 2 positive (ER+/HER2+) breast cancer treated with neoadjuvant chemotherapy and HER2-targeted therapy (NAC+H), and was designed to identify novel biomarkers by correlating gene expression, histology and immunohistochemistry with pathologic response. We performed gene expression profiling on 11 pre-treatment tumors samples: 5 who had no or minimal residual disease residual cancer burden (RCB) score of 0 or 1 and 6 who had significant residual disease (RCB score of 2 or 3). ER2/HER2 postive breast tumors biopsied before neoadjuvant chemotherapy were selected to identify potential biomarkers of pathological complete response (pCR)
2015-09-08 | E-GEOD-67982 | biostudies-arrayexpress
Project description:Non-ablative fractional laser can be used to treat photoaged skin by stimulating the breakdown and regeneration of dermal matrix constituents, such as collagen and elastic fibers. The objective of this study was to validate previously studied molecular mechanisms and explore yet uncharacterized biomarkers underlying the clinical efficacy of non-ablative fractional laser resurfacing.
2022-12-09 | GSE206495 | GEO
Project description:Desmoglein 1 (Dsg1) is a cadherin restricted to stratified tissues of terrestrial vertebrates, which serve as essential physical and immune barriers. Dsg1 loss-of-function mutations in humans result in skin lesions, multiple allergies, and isolated patient keratinocytes exhibit increased pro-allergic cytokine expression. However, the mechanism by which genetic deficiency of Dsg1 causes chronic inflammation is unknown. To determine the systemic response to Dsg1 loss, we deleted the three tandem Dsg1 genes in mice. Whole transcriptome analysis of embryonic Dsg1-/- skin showed a delay in expression of adhesion/differentiation/keratinization genes at E17.5, a subset of which recovered or increased by E18.5. Comparing epidermal transcriptomes from Dsg1-deficient mice and humans revealed a shared IL-17-skewed inflammatory signature. Although the impaired intercellular adhesion observed in Dsg1-/- mice resembles that resulting from anti-Dsg1 pemphigus foliaceus antibodies, pemphigus skin lesions exhibit a weaker IL-17 signature. Consistent with the clinical importance of these findings, treatment of two Dsg1-deficient patients with an IL-12/IL-23 antagonist originally developed for psoriasis resulted in improvement of skin lesions. Thus, beyond impairing the physical barrier, loss of Dsg1 function through gene mutation results in a psoriatic-like inflammatory signature before birth and treatment with a targeted therapy significantly improved skin lesions in patients.
2021-11-25 | GSE189096 | GEO
Project description:Desmoglein 1 (Dsg1) is a cadherin restricted to stratified tissues of terrestrial vertebrates, which serve as essential physical and immune barriers. Dsg1 loss-of-function mutations in humans result in skin lesions, multiple allergies, and isolated patient keratinocytes exhibit increased pro-allergic cytokine expression. However, the mechanism by which genetic deficiency of Dsg1 causes chronic inflammation is unknown. To determine the systemic response to Dsg1 loss, we deleted the three tandem Dsg1 genes in mice. Whole transcriptome analysis of embryonic Dsg1-/- skin showed a delay in expression of adhesion/differentiation/keratinization genes at E17.5, a subset of which recovered or increased by E18.5. Comparing epidermal transcriptomes from Dsg1-deficient mice and humans revealed a shared IL-17-skewed inflammatory signature. Although the impaired intercellular adhesion observed in Dsg1-/- mice resembles that resulting from anti-Dsg1 pemphigus foliaceus antibodies, pemphigus skin lesions exhibit a weaker IL-17 signature. Consistent with the clinical importance of these findings, treatment of two Dsg1-deficient patients with an IL-12/IL-23 antagonist originally developed for psoriasis resulted in improvement of skin lesions. Thus, beyond impairing the physical barrier, loss of Dsg1 function through gene mutation results in a psoriatic-like inflammatory signature before birth and treatment with a targeted therapy significantly improved skin lesions in patients.
2021-11-25 | GSE189095 | GEO
Project description:Desmoglein 1 (Dsg1) is a cadherin restricted to stratified tissues of terrestrial vertebrates, which serve as essential physical and immune barriers. Dsg1 loss-of-function mutations in humans result in skin lesions, multiple allergies, and isolated patient keratinocytes exhibit increased pro-allergic cytokine expression. However, the mechanism by which genetic deficiency of Dsg1 causes chronic inflammation is unknown. To determine the systemic response to Dsg1 loss, we deleted the three tandem Dsg1 genes in mice. Whole transcriptome analysis of embryonic Dsg1-/- skin showed a delay in expression of adhesion/differentiation/keratinization genes at E17.5, a subset of which recovered or increased by E18.5. Comparing epidermal transcriptomes from Dsg1-deficient mice and humans revealed a shared IL-17-skewed inflammatory signature. Although the impaired intercellular adhesion observed in Dsg1-/- mice resembles that resulting from anti-Dsg1 pemphigus foliaceus antibodies, pemphigus skin lesions exhibit a weaker IL-17 signature. Consistent with the clinical importance of these findings, treatment of two Dsg1-deficient patients with an IL-12/IL-23 antagonist originally developed for psoriasis resulted in improvement of skin lesions. Thus, beyond impairing the physical barrier, loss of Dsg1 function through gene mutation results in a psoriatic-like inflammatory signature before birth and treatment with a targeted therapy significantly improved skin lesions in patients.
2021-11-25 | GSE189094 | GEO
Project description:Toxic epidermal necrolysis (TEN) is a fatal cutaneous adverse drug reaction and an emerging public health issue 1-3. Triggered by common medications, patients suffer from fulminant epidermal detachment and long-term sequalae. Although molecular mechanisms driving keratinocyte cytotoxicity have been reported, no effective therapy exists4-6. In recent years, powerful omics technologies have expanded into spatial context and we reasoned that single cell spatial proteomics could uncover novel therapeutic targets in TEN. Applying Deep Visual Proteomics7,8 to formalin fixed paraffin embedded archived skin-tissue biopsies of three types of cutaneous drug reactions with varying severity quantified over 5,000 proteins in keratinocytes and skin-infiltrating immune cells. Most strikingly, this revealed a robust enrichment of Type-I- and -II interferon signature in the immune cell and keratinocyte compartment of TEN patients, along with a drastic activation of pSTAT1. Targeted inhibition with pan-JAK inhibitor (JAKi) Tofacitinib reduced keratinocyte-directed cytotoxicity in a novel live-cell imaging assay, using patient-derived keratinocytes and PBMCs. Furthermore, oral administration of pan-JAKi Tofacitinib or Baricitinib ameliorated clinical and histological disease severity in two distinct mouse models of TEN. This study uncovers the JAK-STAT and interferon signaling pathways as key pathogenic drivers of TEN and demonstrates the potential of targeted JAK inhibition as a curative therapy.
2025-01-13 | PXD044477 | Pride
Project description:Skin constitutes the outer permeability barrier that protects the body from dehydration and a myriad of external assaults. Epidermal keratinocytes act as the first line of innate immune defense, and barrier defects underlie common inflammatory skin diseases. However, the molecular mechanisms that maintain barrier integrity when skin is under challenge to regulate the interplay between epidermal and immune cells are not fully understood. Here we report upregulated expression of transcriptional repressorencoding Ovol1 in epidermal cells of inflamed skin, and its functional importance in maintaining barrier integrity of physically or chemically challenged skin. Following stimulation with imiquimod, Ovol1-deficient mice exhibit significantly aggravated epidermal hyperplasia and psoriasis-like skin inflammation featuring persistent neutrophil accumulation. Using bulk and single-cell RNA-sequencing, we characterize molecular changes in epidermal, fibroblasts, and immune cells that reflect altered epidermal proliferation and differentiation and/or significantly enhanced inflammatory responses as consequences of Ovol1 deletion. We identify both proliferation/differentiation-regulating and neutrophil-attracting chemokine genes as candidate direct targets of Ovol1. Finally, we provide evidence for altered IL-1a signaling in the microenvironment of Ovol1- deficient inflamed skin that functionally contributes to neutrophil accumulation and epidermal hyperplasia. Collectively, our study demonstrates a protective role for an epidermally expressed, disease-linked transcription factor in coordinating robust barrier maintenance with suppression of skin inflammation.
2021-10-27 | GSE158112 | GEO
Project description:Ablative fractional laser treatment is considered the gold standard for skin rejuvenation. In order to understand how fractional laser works to rejuvenate skin, we performed microarray profiling on skin biopsies to identify temporal and dose-response changes in gene expression following fractional laser treatment.
2021-11-07 | GSE168760 | GEO
Project description:We present for the first time the direct molecular effects of microneedling therapy on epidermal keratinocytes and dermal fibroblasts using a standardized 3D skin model. Microneedling treatment resulted in histological alterations and changed the expression of various genes related to epidermal differentiation, inflammation, and dermal remodeling. We speculate that skin microneedling plays a role in dermal remodeling, increases epidermal differentiation, and might also have a direct effect on collagen synthesis. These findings may increase our understanding of the molecular mechanisms of human skin repair induced by microneedling therapy and will allow comparisons with competing applications, such as laser therapies
2018-09-05 | GSE119425 | GEO