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Toxicity of ionizing radiation (IR) in a human induced pluripotent stem cell (hiPSC)-derived 3D early neurodevelopmental model

Toxicity of ionizing radiation (IR) in a human induced pluripotent stem cell (hiPSC)-derived 3D early neurodevelopmental model

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KLATT, Annemarie, Eugenia SALZMANN, Lisanne-Josephin SCHNEIDER, Alexander REIFSCHNEIDER, Milena KORNECK, Patrick HERMLE, Alexander BÜRKLE, Dieter STOLL, Suzanne KADEREIT, 2019. Toxicity of ionizing radiation (IR) in a human induced pluripotent stem cell (hiPSC)-derived 3D early neurodevelopmental model. In: Archives of toxicology. 93(10), pp. 2879-2893. ISSN 0340-5761. eISSN 1432-0738. Available under: doi: 10.1007/s00204-019-02553-z

@article{Klatt2019Toxic-47037, title={Toxicity of ionizing radiation (IR) in a human induced pluripotent stem cell (hiPSC)-derived 3D early neurodevelopmental model}, year={2019}, doi={10.1007/s00204-019-02553-z}, number={10}, volume={93}, issn={0340-5761}, journal={Archives of toxicology}, pages={2879--2893}, author={Klatt, Annemarie and Salzmann, Eugenia and Schneider, Lisanne-Josephin and Reifschneider, Alexander and Korneck, Milena and Hermle, Patrick and Bürkle, Alexander and Stoll, Dieter and Kadereit, Suzanne} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/47037"> <dc:contributor>Hermle, Patrick</dc:contributor> <dc:creator>Klatt, Annemarie</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Korneck, Milena</dc:contributor> <dc:contributor>Schneider, Lisanne-Josephin</dc:contributor> <dcterms:issued>2019</dcterms:issued> <dc:creator>Reifschneider, Alexander</dc:creator> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/47037"/> <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/> <dc:creator>Bürkle, Alexander</dc:creator> <dc:contributor>Kadereit, Suzanne</dc:contributor> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:creator>Hermle, Patrick</dc:creator> <dc:contributor>Salzmann, Eugenia</dc:contributor> <dc:creator>Stoll, Dieter</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-09-26T08:48:33Z</dcterms:available> <dc:creator>Korneck, Milena</dc:creator> <dc:contributor>Klatt, Annemarie</dc:contributor> <dc:creator>Kadereit, Suzanne</dc:creator> <dc:creator>Salzmann, Eugenia</dc:creator> <dc:contributor>Reifschneider, Alexander</dc:contributor> <dc:rights>terms-of-use</dc:rights> <dcterms:title>Toxicity of ionizing radiation (IR) in a human induced pluripotent stem cell (hiPSC)-derived 3D early neurodevelopmental model</dcterms:title> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2019-09-26T08:48:33Z</dc:date> <dc:contributor>Stoll, Dieter</dc:contributor> <dc:contributor>Bürkle, Alexander</dc:contributor> <dcterms:abstract xml:lang="eng">Prenatal brain development is a complex and sensitive process, highly susceptible to environmental influences such as pollutants, stress, malnutrition, drugs, tobacco exposure, or ionizing radiation (IR). Disturbances in development may cause life-long disabilities and diseases, such as ADHD, childhood cancers, cognitive problems, depression, anxiety and more severe developmental disabilities. Due to increasing medical imaging, radiation therapy, natural terrestrial radiation, radioactive pollution and long-distance flights, humans are increasingly exposed to IR. However, data on impact of IR on very early human brain development are scarce, particularly in the very first weeks of gestation. Here we investigated the effects of low-dose X-ray IR (1 Gy) in a 3D early brain developmental model derived from human pluripotent stem cells. In this model very early neural stem cells, neuroectodermal progenitor cells (NEP), were exposed to low-dose IR and direct as well as delayed effects were investigated. Expression of 20 different marker genes crucial for normal neural development was determined 48 h and 9 days post IR (pIR). All but one of the analyzed marker genes were reduced 48 h after IR, and all but seven genes normalized their expression by day 9 pIR. Among the seven markers were genes involved in neurodevelopmental and growth abnormalities. Moreover, we could show that stemness of the NEP was reduced after IR. We were thus able to identify a significant impact of radiation in cells surviving low-dose IR, suggesting that low-dose IR could have a negative impact on the early developing human brain, with potential later detrimental effects.</dcterms:abstract> <dc:creator>Schneider, Lisanne-Josephin</dc:creator> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:language>eng</dc:language> </rdf:Description> </rdf:RDF>

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