TMEM10 Promotes Oligodendrocyte Differentiation and is Expressed by Oligodendrocytes in Human Remyelinating Multiple Sclerosis Plaques
Autor: | David R. Colman, Yasmine Kamen, Timothy E. Kennedy, Alejandro D. Roth, Ajit S. Dhaunchak, Omar de Faria, Tanja Kuhlmann |
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Přispěvatelé: | Roth, Alejandro D [0000-0001-5679-8136], Apollo - University of Cambridge Repository |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Multiple Sclerosis Neurogenesis lcsh:Medicine Biology Article Rats Sprague-Dawley 03 medical and health sciences Myelin Mice 0302 clinical medicine Downregulation and upregulation Gene expression medicine Animals Humans Remyelination lcsh:Science Demyelinating Disorder Cells Cultured Retrospective Studies Multidisciplinary Multiple sclerosis lcsh:R Oligodendrocyte differentiation Cell Differentiation medicine.disease Oligodendrocyte Cell biology Rats Oligodendroglia 030104 developmental biology medicine.anatomical_structure nervous system lcsh:Q 030217 neurology & neurosurgery Myelin Proteins |
Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) |
DOI: | 10.17863/cam.39327 |
Popis: | Oligodendrocyte precursor cells (OPCs) differentiate during postnatal development into myelin-forming oligodendrocytes, in a process distinguished by substantial changes in morphology and the onset of myelin gene expression. A mammalian-specific CNS myelin gene, tmem10, also called Opalin, encodes a type 1 transmembrane protein that is highly upregulated during early stages of OPC differentiation; however, a function for TMEM10 has not yet been identified. Here, consistent with previous studies, we detect TMEM10 protein in mouse brain beginning at ~P10 and show that protein levels continue to increase as oligodendrocytes differentiate and myelinate axons in vivo. We show that constitutive TMEM10 overexpression in the Oli-neu oligodendroglial cell line promotes the expression of the myelin-associated genes MAG, CNP and CGT, whereas TMEM10 knock down in primary OPCs reduces CNP mRNA expression and decreases the percentage of MBP-positive oligodendrocytes that differentiate in vitro. Ectopic TMEM10 expression evokes an increase in process extension and branching, and blocking endogenous TMEM10 expression results in oligodendrocytes with abnormal cell morphology. These findings may have implications for human demyelinating disorders, as oligodendrocytes expressing TMEM10 are detected in human remyelinating multiple sclerosis lesions. Together, our findings provide evidence that TMEM10 promotes oligodendrocyte terminal differentiation and may represent a novel target to promote remyelination in demyelinating disorders. |
Databáze: | OpenAIRE |
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