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Our study aimed to delve deeper into their morphology, transcriptome, and epigenome changes in response to psoriasis-like inflammation. We created a novel cytokine mixture to mimic mild and severe psoriasis-like inflammatory conditions in cultured keratinocytes. Upon induction of inflammation, we observed that the keratinocytes exhibited a mesenchymal-like phenotype, further confirmed by increased VIM mRNA expression and results obtained from confocal microscopy. We performed RNA sequencing to achieve a more global view, revealing 858 and 6987 DEGs in mildly and severely inflamed keratinocytes, respectively. Surprisingly, we found that the transcriptome of mildly inflamed keratinocytes more closely mimicked that of the psoriatic epidermis transcriptome than the severely inflamed keratinocytes. Genes involved in the IL-17 pathway were a major contributor to the similarities of the transcriptomes between mildly inflamed KCs and psoriatic epidermis. Mild and severe inflammation led to the gene regulation of epigenetic modifiers such as HATs, HDACs, DNMTs, and TETs. Immunofluorescence staining revealed distinct 5-hmC patterns in inflamed versus control keratinocytes, and consistently low 5-mC intensity in both groups. However, the global DNA methylation assay detected a tendency of decreased 5-mC levels in inflamed keratinocytes versus controls. This study emphasizes how inflammation severity affects the transcriptomic similarity of keratinocytes to psoriatic epidermis and proves dynamic epigenetic regulation and adaptive morphological changes in inflamed keratinocytes.<\/jats:p>","DOI":"10.3390\/cells12242825","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T04:14:42Z","timestamp":1702440882000},"page":"2825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Unraveling Transcriptome Profile, Epigenetic Dynamics, and Morphological Changes in Psoriasis-like Keratinocytes: \u201cInsights into Similarity with Psoriatic Lesional Epidermis\u201d"],"prefix":"10.3390","volume":"12","author":[{"given":"Ameneh","family":"Ghaffarinia","sequence":"first","affiliation":[{"name":"HCEMM-USZ Skin Research Group, H-6720 Szeged, Hungary"},{"name":"Department of Dermatology and Allergology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Doctoral School of Clinical Medicine, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9722-251X","authenticated-orcid":false,"given":"Szil\u00e1rd","family":"P\u00f3liska","sequence":"additional","affiliation":[{"name":"Genomic Medicine and Bioinformatics Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferhan","family":"Ayaydin","sequence":"additional","affiliation":[{"name":"HCEMM-USZ Functional Cell Biology and Immunology, Advanced Core Facility, H-6728 Szeged, Hungary"},{"name":"Institute of Plant Biology, Biological Research Centre, H-6726 Szeged, 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Allergology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"},{"name":"Systems Immunology Research Group, Institute of Biochemistry, HUN-REN Biological Research Centre, H-6726 Szeged, Hungary"},{"name":"HCEMM-Systems Immunology Research Group, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanni","family":"Balogh","sequence":"additional","affiliation":[{"name":"HCEMM-USZ Skin Research Group, H-6720 Szeged, Hungary"},{"name":"Department of Dermatology and Allergology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, H-6720 Szeged, Hungary"},{"name":"HUN-REN-SZTE Dermatological Research Group, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilla","family":"Erdei","sequence":"additional","affiliation":[{"name":"HCEMM-USZ Skin Research Group, H-6720 Szeged, Hungary"},{"name":"Department of Dermatology and Allergology, Albert Szent-Gy\u00f6rgyi Medical 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