Tape strips capture immune and epidermal hyperplasia markers in the major orphan ichthyoses
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE305032 | GEO | 2026/03/31
REPOSITORIES: GEO
Similar Datasets
Project description:In this study we performed the first global RNA-seq analysis in 54 ichthyosis patients (7 Netherton syndrome/NS, 13 epidermolytic ichthyosis/EI, 16 lamellar ichthyosis/LI, 18 congenital ichthyosiform erythroderma/CIE) and 40 healthy controls. Differentially expressed genes (DEGs) were defined based on fold changes/FCH>2 and false discovery rate/FDR<0.05 criteria. We found robust and significant Th22/Th17 skewing in all subtypes (e.g. IL-17A/C/F, S100A7/8/9/12; p<0.001) with modest changes in Th2 pathway, primarily in NS, and Th1 skewing in CIE.
2022-03-06 | GSE192832 | GEO
Project description:Autosomal recessive congenital ichthyosis (ARCI) is a group of rare inherited skin disorders characterized by remarkable hyperkeratosis. Transglutaminase 1 (TGM1) mutations have been reported to be involved in four different phenotypes of ARCI, including lamellar ichthyosis (LI), non-bullous congenital ichthyosiform erythroderma (NBCIE), bathing suit ichthyosis (BSI), and self-improving collodion ichthyosis (SICI) according to the clinical presentation and histopathology. TGM1 has been found as a defective gene in a large amount of patients with LI and some patients with NBCIE, BSI and SICI. To further understand the effect of TGM1 mutations in epidermal cells development, we performed the transcriptome analysis of HEK293T and HaCaT cells transfected with TGM1 shRNA, TGM1 wild-type and mutant clones. The transcriptomic analysis revealed the effects of TGM1 on cell-cell interaction by suppressing genes involved in the gap junctions, tight junctions and desmosomes. These findings suggested that the TGM1 deficiency disturbed the balance of keratinocytes proliferation and differentiation processes and impaired the epithelial barrier function. The results provided the basis for further understanding on the etiology of ARCI.
2015-12-31 | GSE70859 | GEO
Project description:Autosomal recessive congenital ichthyosis (ARCI) is a group of rare inherited skin disorders characterized by remarkable hyperkeratosis. Transglutaminase 1 (TGM1) mutations have been reported to be involved in four different phenotypes of ARCI, including lamellar ichthyosis (LI), non-bullous congenital ichthyosiform erythroderma (NBCIE), bathing suit ichthyosis (BSI), and self-improving collodion ichthyosis (SICI) according to the clinical presentation and histopathology. TGM1 has been found as a defective gene in a large amount of patients with LI and some patients with NBCIE, BSI and SICI. To further understand the effect of TGM1 mutations in epidermal cells development, we performed the transcriptome analysis of HEK293T and HaCaT cells transfected with TGM1 shRNA, TGM1 wild-type and mutant clones. The transcriptomic analysis revealed the effects of TGM1 on cell-cell interaction by suppressing genes involved in the gap junctions, tight junctions and desmosomes. These findings suggested that the TGM1 deficiency disturbed the balance of keratinocytes proliferation and differentiation processes and impaired the epithelial barrier function. The results provided the basis for further understanding on the etiology of ARCI. To explore the functional impacts on some of the TGM1mutations identified, we cloned and transfected the TGM1 wild type and mutant clones into HEK293T and HaCaT cells. R142C and R348X sequence mutations observed in ARCI (Autosomal recessive congenital ichthyosis) patients were generated. The shRNA targeting TGM1 and a scrambled negative control were obtained from Invitrogen (Carlsbad, CA). The293T and HaCaT cells were transfected with over-expression clones carry either wild-type or mutated TGM1sequence. Cells were harvested 48 hours post-transfection.
2015-12-31 | E-GEOD-70859 | biostudies-arrayexpress
Project description:Background: Skin biopsies represent a gold standard in skin immunology and pathology but can cause pain and induce scarring. Non-invasive techniques will facilitate study recruitment of e.g. patients with pediatric atopic dermatitis (AD), hand eczema or facial dermatitis. Objective: By RNA sequencing, we examined whether the stratum corneum transcriptome in AD skin can be assessed by tape stripping, as compared to the epidermal transcriptome of AD in skin biopsies. To make the procedure clinically relevant tape strips were stored and shipped at room temperature for up to 3 days. Methods: Nine adult Caucasian AD patients and three healthy volunteers were included. Tape samples were collected from non-lesional and lesional skin. Biopsies were collected from lesional skin and were split into epidermis and dermis. Total RNA was extracted, and shotgun sequencing was performed. Results: Shotgun sequencing could be performed on skin cells obtained from two consecutive tape strips which had been stored and shipped at room temperature for up to three days. The most prominent differences between the tape strip and biopsy derived transcriptome were due to structural genes, while established molecular markers of AD, including CCL17, CCL22, IL17A and S100A7-S100A9, were also identified in tape strip samples. Furthermore, the tape strip derived transcriptome showed promise in also analysing the skin microbiome. Conclusion: Our study shows that the stratum corneum (SC) transcriptome of AD can be assessed by tape stripping the skin, supporting that this method may be central in future skin biomarker research.
2020-10-31 | GSE160501 | GEO
Project description:Hand eczema (HE) is a prevalent skin disease. However, classification of HE into different subtypes remains challenging. Limited number of prior studies have employed invasive biopsy-based strategies; yet, studies of the HE proteome using non-invasive tape stripping methodology have not been reported. In this study, we wanted to assess whether global proteomic analysis of skin tape strip samples can be used for sub-classification of HE patients. Tape strips were collected from patients with HE and healthy skin. Liquid chromatography–mass spectrometry (LC/MS) proteomics was performed, and the global protein expression was analyzed. We identified 2,919 proteins in stratum corneum-derived skin cells from tape strip samples. Compared to healthy skin, the lesional samples from HE patients exhibited increased expression of immune-related markers and a decreased expression of structural barrier proteins. The difference between HE subtypes was restricted to the lesional skin areas, and included an increased expression of skin barrier-related proteins independently of the concurrent AD. In conclusion we found, that the non-invasive tape strip method used in combination with LC/MS proteomics can be used for analysis of skin protein expression in HE patients. Thus, the method shows potential for assessing the proteomic differences between subtypes of HE, and biomarker discovery.
2023-04-26 | PXD039665 | Pride
Project description:This pilot study examined gene expression in lesional and non-lesional tape strip samples obtained from 5 patients with immune-checkpoint inhibitor (ICI) eczematous reactions/ICI-Ecz, 3 patients with ICI lichen planus-type reactions/ICI-LP, and 8 patients with atopic dermatitis (AD), as well as from 9 demographically matched healthy controls. Differential expression was defined with |fold-change/FCH|>2 and false discovery rate/FDR<0.1. Significant upregulation in Th1 and Th2, notably in IL4R, was observed in both ICI groups. JAK/STAT upregulation was additionally observed in ICI-Ecz and AD.
2025-05-26 | GSE286907 | GEO
Project description:Autosomal recessive congenital ichthyoses (ARCI) are a group of non-syndromic congenital keratinization disorders including harlequin ichthyosis, lamellar ichthyosis, and congenital ichthyosiform erythroderma with a total prevalence of 1:200,000. Affected individuals who are often born as collodion babies present with generalized scaling of the skin. This reflects a physical compensation for the defective cutaneous permeability barrier underlying all ichthyoses. Inactivity of 12R-lipoxygenase (12R-LOX) is a frequent cause of ARCI. Epidermis-specific conditional knockout of Alox12b encoding 12R-LOX was established in mice using the Cre-Lox system. Tamoxifen-induced Alox12b inactivation in mouse skin caused an ichthyosis-like phenotype. We used microarray to compare the gene expression profile in the epidermis of mice after tamoxifen induced Alox12b inactivation with that of control animals. Inactivation of Alox12b was associated with the upregulation of genes involved in keratinization, cholesterol biosynthesis, and Fc-epsilon receptor signaling.
2019-03-01 | GSE127434 | GEO
Project description:Netherton syndrome (NS) is a rare recessive skin disorder caused by loss-of-function mutations in SPINK5 encoding the protease inhibitor LEKTI. NS patients suffer from a severe skin barrier defect, display inflammatory skin lesions and superficial scaling with atopic manifestations. They can present with typical ichthyosis linearis circumflexa (NS-ILC) or scaly erythroderma (NS-SE). Here we employed a combination of several molecular profiling methods to comprehensively characterize the skin, immune cells and allergic phenotypes of NS-ILC and NS-SE patients. This integrated multi-omic approach revealed abnormal epidermal proliferation and differentiation and IL-17/IL-36 signatures in lesional skin and blood in both NS endotypes. While the molecular profiles of NS-ILC and NS-SE lesional skin were very similar, non-lesional skin of each disease subtype displayed distinctive molecular features. NS-SE non-lesional and lesional epidermis showed activation of the type I IFN signaling pathway, which is involved in skin homeostasis and inflammation. NS-ILC lesional skin differed from NS-ILC non-lesional skin by increased complement activation and neutrophil infiltration. Serum cytokine profiling and immunophenotyping of circulating lymphocytes showed a Th2-driven allergic response in NS-ILC, whereas NS-SE patients displayed mainly a Th9 axis with increased CCL22/MDC and CCL17/TARC serum levels. This study identifies IL-17/IL-36 as predominant signaling axes in both NS endotypes and unveils distinct molecular features characterizing NS-ILC and NS-SE. These results identify new therapeutic targets and could pave the way for precision medicine of NS.
2021-12-31 | GSE164285 | GEO
Project description:Autosomal recessive congenital ichthyoses are a group of non-syndromic congenital keratinization disorders including harlequin ichthyosis, lamellar ichthyosis, and congenital ichthyosiform erythroderma with a total prevalence of 1:200,000. Affected individuals who are often born as collodion babies present with generalized scaling of the skin. This reflects a physical compensation for the defective cutaneous permeability barrier underlying all ichthyoses. Inactivity of 12R-lipoxygenase (12R-LOX) is a frequent cause of ARCI. Mice with targeted inactivation of the 12R-LOX gene Alox12b were established .Heterozygous mutant mice (Alox12b+/−) were bred with 129S6, and their heterozygous offspring were intercrossed to obtain homozygous mutant mice. Homozygous Alox12b knockout mice died within 3 hours after birth owing to defective skin barrier function. We used microarray to compare the gene expression profile in the epidermis of Alox12b-null mice with that of wildtype animals. Inactivation of Alox12b was associated with the upregulation of genes involved in keratinization, cholesterol biosynthesis, and Fc-epsilon receptor signaling.
2019-03-01 | GSE127435 | GEO
Project description:Lamellar Ichthyosis (LI) is a chronic disease, mostly caused by mutations in TGM1 gene, marked by impaired skin barrier formation. No definitive therapies are available and current treatments aim at symptomatic relief. LI mouse models often fail to faithfully replicate the clinical and histopathological features of human skin conditions. To develop advanced therapeutic approaches, as combined ex vivo cell and gene therapy, we established a human cellular model of LI by efficient CRISPR-Cas9-mediated gene ablation of the TGM1 gene in human primary clonogenic keratinocytes. Gene edited cells showed complete absence of Transglutaminase-1 (TG1) expression and recapitulate a hyperkeratotic phenotype with most of the molecular hallmarks of LI in vitro. Using a SINγ-RV vector expressing transgenic TGM1 under the control of its own promoter, we tested an ex vivo gene therapy approach and validate the model of LI as a platform for pre-clinical evaluation studies. Gene-corrected TGM1-null keratinocytes displayed proper TG1 expression, enzymatic activity and cornified envelopes formation, hence restored proper epidermal architecture. Single cell multiomic analysis demonstrated proviral integrations in holoclone-forming epidermal stem cells, which are crucial to epidermal regeneration. This study serves as a proof-of-concept for assessing the potential of this therapeutic approach in treating TGM1 dependent LI.
2024-07-29 | GSE268321 | GEO