RNA-seq result of human skin derived from patients with psoriasis and healthy controls.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE295540 | GEO | 2025/04/25
REPOSITORIES: GEO
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Project description:Disrupted skin barrier due to altered keratinocyte differentiation is common in pathologic conditions such as atopic dermatitis, ichthyosis and psoriasis. However, the molecular cascades governing keratinocyte terminal differentiation are still poorly understood. We have previously demostrated that a dominante mutation in ZNF750 leads to a clinical phenotype that reminiscent of psoriasis and seborrehic dermatitis. We defined ZNF750 as a nuclear effector that is atrongly activated in and essiential for keratinocyte terminal differentiation. ZNF750 knockdown in HaCaT keratinocytes markedly reduced the expression of epidermal late differentiation markers, including gene subsets of epidermal differentiation complex and skin barrier formation such as FLG, LOR, SPINK5, ALOX12B and DSG1, known to be mutated in various human skin diseases. Furthermore, ZNF750 over-expression in undifferentiated cells induced terminal differentiation genes. Thus, ZNF750 is a regulator of keratinocyte terminal differnetiation, and with its downstream targets can serve in future elucidation of therapeutics for common disease of skin barrier Gene expression analysis: To determine the differentaition signature for HaCaT keratinocytes, with ZNF750 gene silencing, total RNA was isolated in biologic triplicates from cells induced to differentiate for twelve days and hybridized to Affymerix Human Gene 1.0 ST arrays.
2012-09-24 | E-GEOD-38039 | biostudies-arrayexpress
Project description:Disrupted skin barrier due to altered keratinocyte differentiation is common in pathologic conditions such as atopic dermatitis, ichthyosis and psoriasis. However, the molecular cascades governing keratinocyte terminal differentiation are still poorly understood. We have previously demonstrated that a dominant mutation in ZNF750 leads to a clinical phenotype that reminiscent of psoriasis and seborrheic dermatitis. We defined ZNF750 as a nuclear effector that is strongly activated in and essential for keratinocyte terminal differentiation. ZNF750 knockdown in HaCaT keratinocytes markedly reduced the expression of epidermal late differentiation markers, including gene subsets of epidermal differentiation complex and skin barrier formation such as FLG, LOR, SPINK5, ALOX12B and DSG1, known to be mutated in various human skin diseases. Furthermore, ZNF750 over-expression in undifferentiated cells induced terminal differentiation genes. Thus, ZNF750 is a regulator of keratinocyte terminal differentiation, and with its downstream targets can serve in future elucidation of therapeutics for common disease of skin barrier
2012-09-24 | GSE38039 | GEO
Project description:To understand the mechanism of disease progression in psoriasis, we defined Asian small plaque psoriasis (small psoriasis) and Asian intermediate plaque psoriasis (intermediate psoriasis) as psoriasis subtypes with limited disease progression, and compared their cellular and molecular signatures with the classic subtype of Western large plaque psoriasis (large psoriasis; GSE30999). Transcriptome analyses in pre-treatment skin biopsies from patients with Asian small and intermediate plaque psoriasis. 12 Asian small plaque psoriasis skin biopsy tissues (7 lesional and 5 non-lesional skin) and 15 Asian intermediate plaque psoriasis skin biopsy tissues (7 lesional and 8 non-lesional skin). GCRMA (using gcrma package from R/Bioconductor) and adjusted for batch effect. The expression data was combined with Western large psoriasis (GSE30999). Using a normalization based upon quantiles, the expression data was normalized based upon a specified normalization distribution of GSE30999 (see publication for GSE67853). The complete dataset representing: (1) 12 Asian small plaque psoriasis Samples, (2) 15 Asian intermediate plaque psoriasis Samples, and (3) 130 Western large plaque psoriasis Samples from GSE30999 (re-processed), is linked below as a supplementary file.
2016-01-10 | E-GEOD-67853 | biostudies-arrayexpress
Project description:To understand the mechanism of disease progression in psoriasis, we defined Asian small plaque psoriasis (small psoriasis) and Asian intermediate plaque psoriasis (intermediate psoriasis) as psoriasis subtypes with limited disease progression, and compared their cellular and molecular signatures with the classic subtype of Western large plaque psoriasis (large psoriasis; GSE30999).
2016-01-10 | GSE67853 | GEO
Project description:Disrupted differentiation is a hallmark of numerous diseases, which in epidermis alone impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for the ZNF750 nuclear protein in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 potently induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation genes. ZNF750 binds the Klf4 promoter and controls its expression. ZNF750 thus provides a direct link between a tissue-specifying factor, p63, and an effector of terminal differentiation, Klf4, and represents a potential future target for disorders of this process. Gene expression analysis: To establish a differentiation signature for primary human keratinocytes, with ZNF750-depleted, and Klf4-depleted, total RNA was isolated in biologic duplicate from cells in different conditions and hybridized to Affymetrix HG-U133 2.0 Plus arrays.
2012-02-15 | E-GEOD-32685 | biostudies-arrayexpress
Project description:Disrupted differentiation is a hallmark of numerous diseases, which in epidermis alone impact >25% of the population. In a search for dominant mediators of differentiation, we defined a requirement for the ZNF750 nuclear protein in terminal epidermal differentiation. ZNF750 controlled genes mutated in numerous human skin diseases, including FLG, LOR, LCE3B, ALOXE3, and SPINK5. ZNF750 potently induced progenitor differentiation via an evolutionarily conserved C2H2 zinc finger motif. The epidermal master regulator, p63, bound the ZNF750 promoter and was necessary for its induction. ZNF750 restored differentiation to p63-deficient tissue, suggesting it acts downstream of p63. A search for functionally important ZNF750 targets via analysis of ZNF750-regulated genes identified KLF4, a transcription factor that activates late epidermal differentiation genes. ZNF750 binds the Klf4 promoter and controls its expression. ZNF750 thus provides a direct link between a tissue-specifying factor, p63, and an effector of terminal differentiation, Klf4, and represents a potential future target for disorders of this process.
2012-02-15 | GSE32685 | GEO
Project description:Immunotherapies targeting IL-17 greatly improve plaque psoriasis. Most previous studies on IL-17 focused on the Th17 immune response, but investigation of the effects of IL-17A on psoriatic epidermal structure are limited. Using an in vitro three-dimensional (3D) human epidermis model, we investigated the effects of IL-17A and IL-17C on morphological changes and gene expression. IL-17A directly suppressed the formation of the granular layer, whereas IL-17C did not. IL-17A significantly downregulated the gene expression of profilaggrin (FLG), which is a major component of keratohyalin granules in the granular layer. Global gene expression analysis of this 3D epidermis model showed that both IL-17A and IL-17C upregulated S100A7A and type 1 interferon-related genes including MX1, IFI44L, XAF1 and IFIT1. However, only IL-17A directly downregulated keratinocyte differentiation-related and cornified envelope-related genes including FLG, LOR, C1ORF68, LCE1E, LCE1B, KRT10, CST6 and RPTN. In conclusion, IL-17A, a systemic inflammatory cytokine, affected keratinization in our 3D epidermis model. In contrast, IL-17C, a locally produced cytokine, did not have strong effects on keratinization. Targeting IL-17A does not only reduce inflammation but it may also directly affect epidermal differentiation in psoriasis.
2020-12-31 | GSE142552 | GEO
Project description:Ustekinumab provides clinical benefit to psoriasis patients, but precise cellular and molecular changes underlying its therapeutic utility are not yet fully understood. To assess differences between ustekinumab responders vs. non responders in modulating specific inflammatory pathways and provide reference data for exploring molecular effects of next-generation interleukin(IL)-17 and IL-23-antagonists in psoriasis.
2019-02-01 | GSE117239 | GEO
Project description:Development of epidermis includes a complicated program of keratinocyte differentiation. Here we study a new membrane LIM-domain containing Zn-finger protein ZNF185 which is expressed in upper layers of human skin and is up-regulated during keratinocyte differentiation in vitro. Interestingly, depletion of ZNF185 causes delay of keratinocyte differentiation with decreased levels of FLG, LOR, LCEs expression.
2018-08-26 | GSE102613 | GEO
Project description:Herein we demonstrate the efficacy of an unbiased proteomics screening approach for studying protein expression changes in the KC-Tie2 psoriasis mouse model, identifying multiple protein expression changes in the mouse and validating these changes in human psoriasis. KC-Tie2 mouse skin samples (n=3) were compared with littermate controls (n=3) using gel-based fractionation followed by label-free protein expression analysis. 5482 peptides mapping to 1281 proteins were identified and quantitated: 105 proteins exhibited fold-changes ≥2.0 including: stefin A1 (average fold change of 342.4 and an average P = 0.0082; cystatin A, human orthologue); slc25a5 (average fold change of 46.2 and an average P = 0.0318); serpinb3b (average fold change of 35.6 and an average P = 0.0345; serpinB1, human orthologue); and kallikrein related peptidase 6 (average fold change of 4.7 and an average P = 0.2474; KLK6). We independently confirmed mouse gene expression-based increases of selected genes including serpinb3b (17.4-fold, P < 0.0001), KLK6 (9.0-fold, P = 0.002), stefin A1 (7.3-fold; P < 0.001) and slc25A5 (1.5-fold; P = 0.05) using qRT-PCR on a second cohort of animals (n=8). Parallel LC/MS/MS analyses on these same samples verified protein-level increases of 1.3-fold (slc25a5; P < 0.05), 29,000-fold (stefinA1; P < 0.01), 322-fold (KLK6; P < 0.0001) between KC-Tie2 and control mice. To underscore the utility and translatability of our combined approach, we analyzed gene and protein expression levels in psoriasis patient skin and primary keratinocytes vs. healthy controls. Increases in gene expression for slc25a5 (1.8-fold), cystatin A (3.0-fold), KLK6 (5.8-fold) and serpinB1 (76-fold; all P < 0.05) were observed between healthy controls and involved lesional psoriasis skin and primary psoriasis keratinocytes. Moreover slc25a5, cystatin A, KLK6 and serpinB1 protein were all increased in lesional psoriasis skin compared to normal skin. These results highlight the usefulness of preclinical disease models using readily-available mouse skin and demonstrate the utility of proteomic approaches for identifying novel peptides/proteins that are differentially regulated in psoriasis that could serve as sources of auto-antigens or provide novel therapeutic targets for the development of new anti-psoriatic treatments.
2014-10-30 | PXD001387 | Pride