Human IPSC-Derived Model to Study Myelin Disruption

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CHESNUT, Megan, Hélène PASCHOUD, Cendrine REPOND, Lena SMIRNOVA, Thomas HARTUNG, Marie-Gabrielle ZURICH, Helena T. HOGBERG, David PAMIES, 2021. Human IPSC-Derived Model to Study Myelin Disruption. In: International Journal of Molecular Sciences (IJMS). MDPI. 22(17), 9473. ISSN 1661-6596. eISSN 1422-0067. Available under: doi: 10.3390/ijms22179473

@article{Chesnut2021-08-31Human-55141, title={Human IPSC-Derived Model to Study Myelin Disruption}, year={2021}, doi={10.3390/ijms22179473}, number={17}, volume={22}, issn={1661-6596}, journal={International Journal of Molecular Sciences (IJMS)}, author={Chesnut, Megan and Paschoud, Hélène and Repond, Cendrine and Smirnova, Lena and Hartung, Thomas and Zurich, Marie-Gabrielle and Hogberg, Helena T. and Pamies, David}, note={Article Number: 9473} }

<rdf:RDF xmlns:dcterms="" xmlns:dc="" xmlns:rdf="" xmlns:bibo="" xmlns:dspace="" xmlns:foaf="" xmlns:void="" xmlns:xsd="" > <rdf:Description rdf:about=""> <dc:contributor>Repond, Cendrine</dc:contributor> <dcterms:title>Human IPSC-Derived Model to Study Myelin Disruption</dcterms:title> <dc:creator>Repond, Cendrine</dc:creator> <dc:contributor>Paschoud, Hélène</dc:contributor> <dc:contributor>Zurich, Marie-Gabrielle</dc:contributor> <dc:creator>Pamies, David</dc:creator> <dc:rights>Attribution 4.0 International</dc:rights> <dc:contributor>Chesnut, Megan</dc:contributor> <dc:creator>Zurich, Marie-Gabrielle</dc:creator> <dc:contributor>Smirnova, Lena</dc:contributor> <dcterms:abstract xml:lang="eng">Myelin is of vital importance to the central nervous system and its disruption is related to a large number of both neurodevelopmental and neurodegenerative diseases. The differences observed between human and rodent oligodendrocytes make animals inadequate for modeling these diseases. Although developing human in vitro models for oligodendrocytes and myelinated axons has been a great challenge, 3D cell cultures derived from iPSC are now available and able to partially reproduce the myelination process. We have previously developed a human iPSC-derived 3D brain organoid model (also called BrainSpheres) that contains a high percentage of myelinated axons and is highly reproducible. Here, we have further refined this technology by applying multiple readouts to study myelination disruption. Myelin was assessed by quantifying immunostaining/confocal microscopy of co-localized myelin basic protein (MBP) with neurofilament proteins as well as proteolipid protein 1 (PLP1). Levels of PLP1 were also assessed by Western blot. We identified compounds capable of inducing developmental neurotoxicity by disrupting myelin in a systematic review to evaluate the relevance of our BrainSphere model for the study of the myelination/demyelination processes. Results demonstrated that the positive reference compound (cuprizone) and two of the three potential myelin disruptors tested (Bisphenol A, Tris(1,3-dichloro-2-propyl) phosphate, but not methyl mercury) decreased myelination, while ibuprofen (negative control) had no effect. Here, we define a methodology that allows quantification of myelin disruption and provides reference compounds for chemical-induced myelin disruption.</dcterms:abstract> <dcterms:hasPart rdf:resource=""/> <dc:creator>Smirnova, Lena</dc:creator> <dc:contributor>Hartung, Thomas</dc:contributor> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:contributor>Pamies, David</dc:contributor> <dcterms:issued>2021-08-31</dcterms:issued> <dc:creator>Chesnut, Megan</dc:creator> <dcterms:isPartOf rdf:resource=""/> <dc:creator>Hogberg, Helena T.</dc:creator> <dc:contributor>Hogberg, Helena T.</dc:contributor> <dc:date rdf:datatype="">2021-10-05T09:44:13Z</dc:date> <dcterms:rights rdf:resource=""/> <dspace:hasBitstream rdf:resource=""/> <dc:creator>Hartung, Thomas</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dspace:isPartOfCollection rdf:resource=""/> <dc:creator>Paschoud, Hélène</dc:creator> <dcterms:available rdf:datatype="">2021-10-05T09:44:13Z</dcterms:available> <bibo:uri rdf:resource=""/> <dc:language>eng</dc:language> </rdf:Description> </rdf:RDF>

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