Limited TCF7L2 expression in MS lesions.

Multiple sclerosis is the most frequent demyelinating disease in the human CNS characterized by inflammation, demyelination, relative axonal loss and gliosis. Remyelination occurs, but is frequently absent or restricted to a small remyelinated rim at the lesion border. Impaired differentiation of ol...

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Autores principales:	Alexander Lürbke, Karin Hagemeier, Qiao-Ling Cui, Imke Metz, Wolfgang Brück, Jack Antel, Tanja Kuhlmann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7f48f265fe544222a33556836fbfcc39
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spelling	oai:doaj.org-article:7f48f265fe544222a33556836fbfcc392021-11-18T08:58:43ZLimited TCF7L2 expression in MS lesions.1932-620310.1371/journal.pone.0072822https://doaj.org/article/7f48f265fe544222a33556836fbfcc392013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23977356/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Multiple sclerosis is the most frequent demyelinating disease in the human CNS characterized by inflammation, demyelination, relative axonal loss and gliosis. Remyelination occurs, but is frequently absent or restricted to a small remyelinated rim at the lesion border. Impaired differentiation of oligodendroglial precursor cells is one factor contributing to limited remyelination, especially in chronic MS. TCF7L2 is an oligodendroglial transcription factor regulating myelin gene expression during developmental myelination as well as remyelination. TCF7L2 binds to co-effectors such as β-catenin or histone deacetylases and thereby activates or inhibits the transcription of downstream genes involved in oligodendroglial differentiation. To determine whether TCF7L2 can be used as a marker for differentiating or myelinating oligodendrocytes, we analyzed the expression patterns of TCF7L2 during myelination and remyelination in human and murine CNS tissue samples. Here, we demonstrate that marked expression of TCF7L2 in oligodendrocytes is restricted to a well defined time period during developmental myelination in human and mouse CNS tissue samples. In demyelinating diseases, such as multiple sclerosis, TCF7L2 is reexpressed in oligodendrocytes in a subset of MS patients, but is also present in tissue samples from patients with non-demyelinating, inflammatory diseases. Furthermore, TCF7L2 expression was also detected in astrocytes. HDAC2, a potential binding partner of TCF7L2 that promotes oligodendroglial differentiation and myelination, is expressed in the majority of oligodendrocytes in controls and MS tissue samples. In summary, our data demonstrate that the expression of TCF7L2 in oligodendrocytes is limited to a certain differentiation stage; however the expression of TCF7L2 is neither restricted to the oligodendroglial lineage nor to (re-)myelinating conditions.Alexander LürbkeKarin HagemeierQiao-Ling CuiImke MetzWolfgang BrückJack AntelTanja KuhlmannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72822 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexander Lürbke Karin Hagemeier Qiao-Ling Cui Imke Metz Wolfgang Brück Jack Antel Tanja Kuhlmann Limited TCF7L2 expression in MS lesions.
description	Multiple sclerosis is the most frequent demyelinating disease in the human CNS characterized by inflammation, demyelination, relative axonal loss and gliosis. Remyelination occurs, but is frequently absent or restricted to a small remyelinated rim at the lesion border. Impaired differentiation of oligodendroglial precursor cells is one factor contributing to limited remyelination, especially in chronic MS. TCF7L2 is an oligodendroglial transcription factor regulating myelin gene expression during developmental myelination as well as remyelination. TCF7L2 binds to co-effectors such as β-catenin or histone deacetylases and thereby activates or inhibits the transcription of downstream genes involved in oligodendroglial differentiation. To determine whether TCF7L2 can be used as a marker for differentiating or myelinating oligodendrocytes, we analyzed the expression patterns of TCF7L2 during myelination and remyelination in human and murine CNS tissue samples. Here, we demonstrate that marked expression of TCF7L2 in oligodendrocytes is restricted to a well defined time period during developmental myelination in human and mouse CNS tissue samples. In demyelinating diseases, such as multiple sclerosis, TCF7L2 is reexpressed in oligodendrocytes in a subset of MS patients, but is also present in tissue samples from patients with non-demyelinating, inflammatory diseases. Furthermore, TCF7L2 expression was also detected in astrocytes. HDAC2, a potential binding partner of TCF7L2 that promotes oligodendroglial differentiation and myelination, is expressed in the majority of oligodendrocytes in controls and MS tissue samples. In summary, our data demonstrate that the expression of TCF7L2 in oligodendrocytes is limited to a certain differentiation stage; however the expression of TCF7L2 is neither restricted to the oligodendroglial lineage nor to (re-)myelinating conditions.
format	article
author	Alexander Lürbke Karin Hagemeier Qiao-Ling Cui Imke Metz Wolfgang Brück Jack Antel Tanja Kuhlmann
author_facet	Alexander Lürbke Karin Hagemeier Qiao-Ling Cui Imke Metz Wolfgang Brück Jack Antel Tanja Kuhlmann
author_sort	Alexander Lürbke
title	Limited TCF7L2 expression in MS lesions.
title_short	Limited TCF7L2 expression in MS lesions.
title_full	Limited TCF7L2 expression in MS lesions.
title_fullStr	Limited TCF7L2 expression in MS lesions.
title_full_unstemmed	Limited TCF7L2 expression in MS lesions.
title_sort	limited tcf7l2 expression in ms lesions.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7f48f265fe544222a33556836fbfcc39
work_keys_str_mv	AT alexanderlurbke limitedtcf7l2expressioninmslesions AT karinhagemeier limitedtcf7l2expressioninmslesions AT qiaolingcui limitedtcf7l2expressioninmslesions AT imkemetz limitedtcf7l2expressioninmslesions AT wolfgangbruck limitedtcf7l2expressioninmslesions AT jackantel limitedtcf7l2expressioninmslesions AT tanjakuhlmann limitedtcf7l2expressioninmslesions
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Limited TCF7L2 expression in MS lesions.

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