MicroRNAs dysregulated in multiple sclerosis affect the differentiation of CG-4 cells, an oligodendrocyte progenitor cell line
IntroductionDemyelination is one of the hallmarks of multiple sclerosis (MS). While remyelination occurs during the disease, it is incomplete from the start and strongly decreases with its progression, mainly due to the harm to oligodendrocyte progenitor cells (OPCs), causing irreversible neurologic...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2024.1336439/full |
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| author | Océane Perdaens Pauline Bottemanne Vincent van Pesch Vincent van Pesch |
| author_facet | Océane Perdaens Pauline Bottemanne Vincent van Pesch Vincent van Pesch |
| author_sort | Océane Perdaens |
| collection | DOAJ |
| description | IntroductionDemyelination is one of the hallmarks of multiple sclerosis (MS). While remyelination occurs during the disease, it is incomplete from the start and strongly decreases with its progression, mainly due to the harm to oligodendrocyte progenitor cells (OPCs), causing irreversible neurological deficits and contributing to neurodegeneration. Therapeutic strategies promoting remyelination are still very preliminary and lacking within the current treatment panel for MS.MethodsIn a previous study, we identified 21 microRNAs dysregulated mostly in the CSF of relapsing and/or remitting MS patients. In this study we transfected the mimics/inhibitors of several of these microRNAs separately in an OPC cell line, called CG-4. We aimed (1) to phenotypically characterize their effect on OPC differentiation and (2) to identify corroborating potential mRNA targets via immunocytochemistry, RT-qPCR analysis, RNA sequencing, and Gene Ontology enrichment analysis.ResultsWe observed that the majority of 13 transfected microRNA mimics decreased the differentiation of CG-4 cells. We demonstrate, by RNA sequencing and independent RT-qPCR analyses, that miR-33-3p, miR-34c-5p, and miR-124-5p arrest OPC differentiation at a late progenitor stage and miR-145-5p at a premyelinating stage as evidenced by the downregulation of premyelinating oligodendrocyte (OL) [Tcf7l2, Cnp (except for miR-145-5p)] and mature OL (Plp1, Mbp, and Mobp) markers, whereas only miR-214-3p promotes OPC differentiation. We further propose a comprehensive exploration of their change in cell fate through Gene Ontology enrichment analysis. We finally confirm by RT-qPCR analyses the downregulation of several predicted mRNA targets for each microRNA that possibly support their effect on OPC differentiation by very distinctive mechanisms, of which some are still unexplored in OPC/OL physiology.ConclusionmiR-33-3p, miR-34c-5p, and miR-124-5p arrest OPC differentiation at a late progenitor stage and miR-145-5p at a premyelinating stage, whereas miR-214-3p promotes the differentiation of CG-4 cells. We propose several potential mRNA targets and hypothetical mechanisms by which each microRNA exerts its effect. We hereby open new perspectives in the research on OPC differentiation and the pathophysiology of demyelination/remyelination, and possibly even in the search for new remyelinating therapeutic strategies in the scope of MS. |
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| id | doaj.art-53ec7d09a17a4d18a5df94f7c2add396 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-07T19:44:22Z |
| publishDate | 2024-02-01 |
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| spelling | doaj.art-53ec7d09a17a4d18a5df94f7c2add3962024-02-29T04:33:36ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022024-02-011810.3389/fncel.2024.13364391336439MicroRNAs dysregulated in multiple sclerosis affect the differentiation of CG-4 cells, an oligodendrocyte progenitor cell lineOcéane Perdaens0Pauline Bottemanne1Vincent van Pesch2Vincent van Pesch3Neurochemistry Group, Institute of NeuroScience, Université catholique de Louvain (UCLouvain), Brussels, BelgiumBioanalysis and Pharmacology of Bioactive Lipids, Louvain Drug Research Institute, Université catholique de Louvain (UCLouvain), Brussels, BelgiumNeurochemistry Group, Institute of NeuroScience, Université catholique de Louvain (UCLouvain), Brussels, BelgiumDepartment of Neurology, Cliniques universitaires Saint-Luc, Université catholique de Louvain (UCLouvain), Brussels, BelgiumIntroductionDemyelination is one of the hallmarks of multiple sclerosis (MS). While remyelination occurs during the disease, it is incomplete from the start and strongly decreases with its progression, mainly due to the harm to oligodendrocyte progenitor cells (OPCs), causing irreversible neurological deficits and contributing to neurodegeneration. Therapeutic strategies promoting remyelination are still very preliminary and lacking within the current treatment panel for MS.MethodsIn a previous study, we identified 21 microRNAs dysregulated mostly in the CSF of relapsing and/or remitting MS patients. In this study we transfected the mimics/inhibitors of several of these microRNAs separately in an OPC cell line, called CG-4. We aimed (1) to phenotypically characterize their effect on OPC differentiation and (2) to identify corroborating potential mRNA targets via immunocytochemistry, RT-qPCR analysis, RNA sequencing, and Gene Ontology enrichment analysis.ResultsWe observed that the majority of 13 transfected microRNA mimics decreased the differentiation of CG-4 cells. We demonstrate, by RNA sequencing and independent RT-qPCR analyses, that miR-33-3p, miR-34c-5p, and miR-124-5p arrest OPC differentiation at a late progenitor stage and miR-145-5p at a premyelinating stage as evidenced by the downregulation of premyelinating oligodendrocyte (OL) [Tcf7l2, Cnp (except for miR-145-5p)] and mature OL (Plp1, Mbp, and Mobp) markers, whereas only miR-214-3p promotes OPC differentiation. We further propose a comprehensive exploration of their change in cell fate through Gene Ontology enrichment analysis. We finally confirm by RT-qPCR analyses the downregulation of several predicted mRNA targets for each microRNA that possibly support their effect on OPC differentiation by very distinctive mechanisms, of which some are still unexplored in OPC/OL physiology.ConclusionmiR-33-3p, miR-34c-5p, and miR-124-5p arrest OPC differentiation at a late progenitor stage and miR-145-5p at a premyelinating stage, whereas miR-214-3p promotes the differentiation of CG-4 cells. We propose several potential mRNA targets and hypothetical mechanisms by which each microRNA exerts its effect. We hereby open new perspectives in the research on OPC differentiation and the pathophysiology of demyelination/remyelination, and possibly even in the search for new remyelinating therapeutic strategies in the scope of MS.https://www.frontiersin.org/articles/10.3389/fncel.2024.1336439/fullmultiple sclerosismicroRNAmiR-33-3pmiR-34c-5pmiR-124-5pmiR-214-3p |
| spellingShingle | Océane Perdaens Pauline Bottemanne Vincent van Pesch Vincent van Pesch MicroRNAs dysregulated in multiple sclerosis affect the differentiation of CG-4 cells, an oligodendrocyte progenitor cell line Frontiers in Cellular Neuroscience multiple sclerosis microRNA miR-33-3p miR-34c-5p miR-124-5p miR-214-3p |
| title | MicroRNAs dysregulated in multiple sclerosis affect the differentiation of CG-4 cells, an oligodendrocyte progenitor cell line |
| title_full | MicroRNAs dysregulated in multiple sclerosis affect the differentiation of CG-4 cells, an oligodendrocyte progenitor cell line |
| title_fullStr | MicroRNAs dysregulated in multiple sclerosis affect the differentiation of CG-4 cells, an oligodendrocyte progenitor cell line |
| title_full_unstemmed | MicroRNAs dysregulated in multiple sclerosis affect the differentiation of CG-4 cells, an oligodendrocyte progenitor cell line |
| title_short | MicroRNAs dysregulated in multiple sclerosis affect the differentiation of CG-4 cells, an oligodendrocyte progenitor cell line |
| title_sort | micrornas dysregulated in multiple sclerosis affect the differentiation of cg 4 cells an oligodendrocyte progenitor cell line |
| topic | multiple sclerosis microRNA miR-33-3p miR-34c-5p miR-124-5p miR-214-3p |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2024.1336439/full |
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