A Hairless Mouse Model for Vitiligo: Enhancing Preclinical Therapeutic Evaluation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1288449 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Vitiligo is an autoimmune disease that targets melanocytes, and preclinical models of the disease can strongly promote the development of new treatments. This study introduces a vitiligo model using hairless hk14-SCF Tg mice, whose melanocyte distribution closely mimics human skin, enabling comprehensive therapeutic evaluation. Two methods were used to induce vitiligo: (1) hairless hk14-SCF Tg mice received bone marrow-derived dendritic cells (BMDCs) pulsed with the melanocyte-specific peptide gp100 and CD8+ T cells targeting gp100 (PMEL CD8+ T cells), and (2) hk14-SCF Tg mice were crossbred with PMEL TCR transgenic mice without additional treatment. Skin samples were subsequently analyzed using immunohistochemistry, flow cytometry, bulk RNA sequencing, and cytokine assays, confirming that the mechanisms that drive vitiligo in this model closely resemble those of prior mouse models and vitiligo patients. Various treatments— including ultraviolet irradiation, topical corticosteroids, and a JAK inhibitor—were tested and all significantly reduced vitiligo-affected areas, as verified through objective ImageJ analysis. In conclusion, this model addresses key limitations of previous models, offering a robust platform for preclinical treatment evaluation and potentially accelerating clinical translation.
2025-07-14 | GSE302067 | GEO
Project description:Investigate the gene expression change in the blood of segmental vitiligo, generalized vitiligo and healthy individual.
2016-04-08 | GSE80009 | GEO
Project description:Vitiligo is an acquired depigmentation of the skin inducing a marked alteration of the quality of life of affected individuals. Halting the disease progression and repigmenting the lesional skin represent the two faces of the therapeutic challenge in vitiligo. So far, none of them has been successfully addressed. Oxidative stress and immune system in genetically predisposed individuals participate to the complex pathophysiology of vitiligo. We performed a transcriptome and proteomic analysis on lesional, perilesional and non-depigmented skin of vitiligo patients compared to matched skin controls of healthy subjects. Our results show that the WNT pathway, implicated in melanocytes differentiation, was found to be altered in vitiligo skin. We demonstrated that the oxidative stress decreases WNT expression/activation in keratinocytes and in melanocytes. We developed an ex vivo skin model that remains functional up to 15 days. We then confirmed the decreased activation of the WNT pathway in human skin subjected to oxidative stress. Finally, using pharmacological agents that activate the WNT pathway, we treated the ex vivo depigmented skins from vitiligo patients and successfully induced the differentiation of resident stem cells into pre-melanocytes supporting further exploration of WNT activators to repigment vitiligo lesions. Total of 40 chips. 10 patients (3 biospies per patient: 1 lesional , 1 perilesional and 1 non lesional) ; 10 healthy volunteers (1biopsy in matched anatomical areas)
2015-10-01 | E-GEOD-65127 | biostudies-arrayexpress
Project description:Vitiligo is an acquired depigmentation of the skin inducing a marked alteration of the quality of life of affected individuals. Halting the disease progression and repigmenting the lesional skin represent the two faces of the therapeutic challenge in vitiligo. So far, none of them has been successfully addressed. Oxidative stress and immune system in genetically predisposed individuaLesionalparticipate to the complex pathophysiology of vitiligo. We performed a transcriptome and proteomic analysis on lesional, perilesional and non-depigmented skin of vitiligo patients compared to matched skin controLesionalof healthy subjects. Our results show that the WNT pathway, implicated in melanocytes differentiation, was found to be altered in vitiligo skin. We demonstrated that the oxidative stress decreases WNT expression/activation in keratinocytes and in melanocytes. We developed an ex vivo skin model that remains functional up to 15 days. We then confirmed the decreased activation of the WNT pathway in human skin subjected to oxidative stress. Finally, using pharmacological agents that activate the WNT pathway, we treated the ex vivo depigmented skins from vitiligo patients and successfully induced the differentiation of resident stem celLesionalinto pre-melanocytes supporting further exploration of WNT activators to repigment vitiligo lesions.
2015-10-01 | GSE65127 | GEO
Project description:Skin samples from mice in a model of vitiligo were selected for gene expression profiling in order to identify active inflammatory pathways. Total RNA isolated from 6 mouse samples from fresh skin, 3 from vitiligo mice and 3 from control mice.
2013-12-12 | E-GEOD-53147 | biostudies-arrayexpress
Project description:Several co-repressors interact directly with the DNA-binding protein CSL [Su(H) in Drosophila] and are proposed to keep target genes silenced in the absence of Notch activity. To investigate co-repressor activity in the context of this well defined signalling pathway, we analysed the genome-wide binding profile of the best-characterized CSL co-repressor in Drosophila, Hairless, in Kc cells and in wing imaginal discs. The binding profile in wing discs of a second CSL interacting repressor, SMRTER, was also analysed. There was significant overlap between Hairless and Su(H), both in Kc cells and in wing discs, where they were predominantly found in chromatin with active enhancer marks. The Hairless complex was widely present at some Notch regulated enhancers in the wing disc,but no binding was detected at others, indicating that it is not essential for silencing per se. Analysis of target enhancers confirmed differential requirements for Hairless. SMRTER binding significantly overlapped with Hairless, rather than complementing it, and many enhancers were apparently co-bound by both factors. Our analysis indicates that the actions of Hairless and SMRTER gate the enhancers to Notch activity and to Ecdysone signalling respectively, to ensure that the appropriate levels and timing of target gene expression are achieved.
2017-12-31 | GSE97597 | GEO
Project description:Vitiligo skin samples with an active inflammatory infiltrate were selected for gene expression profiling in order to identify inflammatory pathways that drive depigmentation in vitiligo. Total RNA was isolated from 10 deidentified human samples from formalin fixed, paraffin-embedded skin, 5 from vitiligo patients and 5 from controls. Control skin was age- and site-matched excision tips without pathology.
2013-12-12 | E-GEOD-53146 | biostudies-arrayexpress
Project description:Click chemistry enables comprehensive preclinical evaluation of targeted epigenetic therapies
| PRJNA348447 | ENA
Project description:The aim of this study was to investigate the differential expression of long non-coding RNAs (lncRNAs) in T cells from patients with vitiligo and their roles in the pathogenesis of vitiligo. The expression profiles of the RNA transcripts in T cells from three patients with vitiligo and three controls were conducted using microarray analysis. These aberrantly-expressed genes were further validated using T cells from 41 patients with vitiligo and 28 controls. The biologic function of the specific lncRNAs was investigated using transfection, RNA pull-down assay plus proteomic approach and Western blotting. As the results, the expression levels of 134 genes, were significantly increased, whereas the expression levels 142 genes were significantly decreased in T cells from patients with vitiligo compared with the controls. After selection and validation, the expression levels of 11 genes increased and two genes decreased in T cells from patients with vitiligo. We confirmed that LOC100506314 could interact with the signal transducer and activator of transcription 3 (STAT3) and macrophage migration inhibitory factor (MIF). The transfection of LOC100506314 could suppress STAT3, AKT, and ERK phosphorylation and nuclear protein levels of p65. Finally, overexpressed LOC100506314 decreased the T cell expression of IL-6 and IL-17. In conclusion, among the lncRNAs, we found that the expression levels of LOC100506314 were increased in T cells from patients with vitiligo. LOC100506314 could bind to STAT3 and MIF and suppress the expression of IL-6 and IL-17 through the inhibition of the STAT3, AKT, ERK, and NF-κB pathway. Increased the expression of LOC100506314 in T cells could be a potential therapeutic strategy for vitiligo.
2023-09-27 | GSE205751 | GEO
Project description:Several co-repressors interact directly with the DNA-binding protein CSL [Su(H) in Drosophila] and are proposed to keep target genes silenced in the absence of Notch activity. To investigate co-repressor activity in the context of this well defined signalling pathway, we analysed the genome-wide binding profile of the best-characterized CSL co-repressor in Drosophila, Hairless, in Kc cells and in wing imaginal discs. The binding profile in wing discs of a second CSL interacting repressor, SMRTER, was also analysed. There was significant overlap between Hairless and Su(H), both in Kc cells and in wing discs, where they were predominantly found in chromatin with active enhancer marks. The Hairless complex was widely present at some Notch regulated enhancers in the wing disc,but no binding was detected at others, indicating that it is not essential for silencing per se. Analysis of target enhancers confirmed differential requirements for Hairless. SMRTER binding significantly overlapped with Hairless, rather than complementing it, and many enhancers were apparently co-bound by both factors. Our analysis indicates that the actions of Hairless and SMRTER gate the enhancers to Notch activity and to Ecdysone signalling respectively, to ensure that the appropriate levels and timing of target gene expression are achieved.
2017-12-31 | GSE97599 | GEO