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Through conducting a transcriptomic analysis of microarray studies on the demyelination\u2013remyelination cuprizone model and using human samples of multiple sclerosis (MS), we identified molecules involved in this crosstalk. Differentially expressed genes (DEGs) of specific regions\/cell types were detected in GEO transcriptomic raw data after cuprizone treatment and in MS samples, followed by functional analysis with GO terms and WikiPathways. Additionally, microglia\u2013OPC crosstalk between microglia ligands, OPC receptors and target genes was examined with the NicheNet model. We identified 108 and 166 DEGs in the demyelinated corpus callosum (CC) at 2 and 4 weeks of cuprizone treatment; 427 and 355 DEGs in the remyelinated (4 weeks of cuprizone treatment + 14 days of normal diet) compared to 2- and 4-week demyelinated CC; 252 DEGs in MS samples and 2730 and 12 DEGs in OPC and microglia of 4-week demyelinated CC. At this time point, we found 95 common DEGs in the CC and OPCs, and one common DEG in microglia and OPCs, mostly associated with myelin and lipid metabolism. Crosstalk analysis identified 47 microglia ligands, 43 OPC receptors and 115 OPC target genes, all differentially expressed in cuprizone-treated samples and associated with myelination. Our differential expression pipeline identified demyelination\/remyelination transcriptomic biomarkers in studies using diverse platforms and cell types\/tissues. Cellular crosstalk analysis yielded novel markers of microglia ligands, OPC receptors and target genes.<\/jats:p>","DOI":"10.3390\/ijms232314868","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T04:01:33Z","timestamp":1669608093000},"page":"14868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Deciphering the Genetic Crosstalk between Microglia and Oligodendrocyte Precursor Cells during Demyelination and Remyelination Using Transcriptomic Data"],"prefix":"10.3390","volume":"23","author":[{"given":"Jennifer","family":"Enrich-Bengoa","sequence":"first","affiliation":[{"name":"Biophysics Unit, Department of Biochemistry and Molecular Biology, School of Medicine, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Catalonia, Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Manich","sequence":"additional","affiliation":[{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Catalonia, Spain"},{"name":"Medical Histology Unit, Department of Cell Biology, Physiology and Immunology, School of Medicine, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene R.","family":"D\u00e9gano","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red of Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Registre Giron\u00ed del Cor (REGICOR) Study Group, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Catalonia, Spain"},{"name":"Faculty of Medicine, University of Vic-Central University of Catalonia, 08500 Vic, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3457-0875","authenticated-orcid":false,"given":"Alex","family":"Per\u00e1lvarez-Mar\u00edn","sequence":"additional","affiliation":[{"name":"Biophysics Unit, Department of Biochemistry and Molecular Biology, School of Medicine, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Catalonia, Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1177\/1352458520970841","article-title":"Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition","volume":"26","author":"Walton","year":"2020","journal-title":"Mult. 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