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Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems

Postmortem studies in patients with schizophrenia (SCZ) have revealed deficits in myelination, abnormalities in myelin gene expression and altered numbers of oligodendrocytes in the brain. However, gaining mechanistic insight into oligodendrocyte (OL) dysfunction and its contribution to SCZ has been...

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Autores principales: Raabe, Florian J., Galinski, Sabrina, Papiol, Sergi, Falkai, Peter G., Schmitt, Andrea, Rossner, Moritz J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242875/
https://www.ncbi.nlm.nih.gov/pubmed/30451850
http://dx.doi.org/10.1038/s41537-018-0066-4
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author Raabe, Florian J.
Galinski, Sabrina
Papiol, Sergi
Falkai, Peter G.
Schmitt, Andrea
Rossner, Moritz J.
author_facet Raabe, Florian J.
Galinski, Sabrina
Papiol, Sergi
Falkai, Peter G.
Schmitt, Andrea
Rossner, Moritz J.
author_sort Raabe, Florian J.
collection PubMed
description Postmortem studies in patients with schizophrenia (SCZ) have revealed deficits in myelination, abnormalities in myelin gene expression and altered numbers of oligodendrocytes in the brain. However, gaining mechanistic insight into oligodendrocyte (OL) dysfunction and its contribution to SCZ has been challenging because of technical hurdles. The advent of individual patient-derived human-induced pluripotent stem cells (hiPSCs), combined with the generation of in principle any neuronal and glial cell type, including OLs and oligodendrocyte precursor cells (OPCs), holds great potential for understanding the molecular basis of the aetiopathogenesis of genetically complex psychiatric diseases such as SCZ and could pave the way towards personalized medicine. The development of neuronal and glial co-culture systems now appears to enable the in vitro study of SCZ-relevant neurobiological endophenotypes, including OL dysfunction and myelination, with unprecedented construct validity. Nonetheless, the meaningful stratification of patients before the subsequent functional analyses of patient-derived cell systems still represents an important bottleneck. Here, to improve the predictive power of ex vivo disease modelling we propose using hiPSC technology to focus on representatives of patient subgroups stratified for genomic and/or phenomic features and neurobiological cell systems. Therefore, this review will outline the evidence for the involvement of OPCs/OLs in SCZ in the context of their proposed functions, including myelination and axon support, the implications for hiPSC-based cellular disease modelling and potential strategies for patient selection.
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spelling pubmed-62428752018-11-26 Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems Raabe, Florian J. Galinski, Sabrina Papiol, Sergi Falkai, Peter G. Schmitt, Andrea Rossner, Moritz J. NPJ Schizophr Review Article Postmortem studies in patients with schizophrenia (SCZ) have revealed deficits in myelination, abnormalities in myelin gene expression and altered numbers of oligodendrocytes in the brain. However, gaining mechanistic insight into oligodendrocyte (OL) dysfunction and its contribution to SCZ has been challenging because of technical hurdles. The advent of individual patient-derived human-induced pluripotent stem cells (hiPSCs), combined with the generation of in principle any neuronal and glial cell type, including OLs and oligodendrocyte precursor cells (OPCs), holds great potential for understanding the molecular basis of the aetiopathogenesis of genetically complex psychiatric diseases such as SCZ and could pave the way towards personalized medicine. The development of neuronal and glial co-culture systems now appears to enable the in vitro study of SCZ-relevant neurobiological endophenotypes, including OL dysfunction and myelination, with unprecedented construct validity. Nonetheless, the meaningful stratification of patients before the subsequent functional analyses of patient-derived cell systems still represents an important bottleneck. Here, to improve the predictive power of ex vivo disease modelling we propose using hiPSC technology to focus on representatives of patient subgroups stratified for genomic and/or phenomic features and neurobiological cell systems. Therefore, this review will outline the evidence for the involvement of OPCs/OLs in SCZ in the context of their proposed functions, including myelination and axon support, the implications for hiPSC-based cellular disease modelling and potential strategies for patient selection. Nature Publishing Group UK 2018-11-19 /pmc/articles/PMC6242875/ /pubmed/30451850 http://dx.doi.org/10.1038/s41537-018-0066-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Review Article
Raabe, Florian J.
Galinski, Sabrina
Papiol, Sergi
Falkai, Peter G.
Schmitt, Andrea
Rossner, Moritz J.
Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems
title Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems
title_full Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems
title_fullStr Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems
title_full_unstemmed Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems
title_short Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems
title_sort studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242875/
https://www.ncbi.nlm.nih.gov/pubmed/30451850
http://dx.doi.org/10.1038/s41537-018-0066-4
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