Neuronal developmental gene and miRNA signatures induced by histone deacetylase inhibitors in human embryonic stem cells

Lade...
Vorschaubild
Dateien
Meganathan_0-291341.pdf
Meganathan_0-291341.pdfGröße: 3.33 MBDownloads: 290
Datum
2015
Autor:innen
Meganathan, Kesavan
Jagtap, Smita
Srinivasan, Sureshkumar Perumal
Wagh, Vilas
Hescheler, Jürgen
Hengstler, Jan
Sachinidis, Agapios
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
ArXiv-ID
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Gold
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Zusammenfassung

Human embryonic stem cells (hESCs) may be applied to develop human-relevant sensitive in vitro test systems for monitoring developmental toxicants. The aim of this study was to identify potential developmental toxicity mechanisms of the histone deacetylase inhibitors (HDAC) valproic acid (VPA), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) relevant to the in vivo condition using a hESC model in combination with specific differentiation protocols and genome-wide gene expression and microRNA profiling. Analysis of the gene expression data showed that VPA repressed neural tube and dorsal forebrain (OTX2, ISL1, EMX2 and SOX10)-related transcripts. In addition, VPA upregulates axonogenesis and ventral forebrain-associated genes, such as SLIT1, SEMA3A, DLX2/4 and GAD2. HDACi-induced expression of miR-378 and knockdown of miR-378 increases the expression of OTX2 and EMX2, which supports our hypothesis that HDACi targets forebrain markers through miR-378. In conclusion, multilineage differentiation in vitro test system is very sensitive for monitoring molecular activities relevant to in vivo neuronal developmental toxicity. Moreover, miR-378 seems to repress the expression of the OTX2 and EMX2 and therefore could be a regulator of the development of neural tube and dorsal forebrain neurons.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690MEGANATHAN, Kesavan, Smita JAGTAP, Sureshkumar Perumal SRINIVASAN, Vilas WAGH, Jürgen HESCHELER, Jan HENGSTLER, Marcel LEIST, Agapios SACHINIDIS, 2015. Neuronal developmental gene and miRNA signatures induced by histone deacetylase inhibitors in human embryonic stem cells. In: Cell Death and Disease. 2015, 6, e1756. eISSN 2041-4889. Available under: doi: 10.1038/cddis.2015.121
BibTex
@article{Meganathan2015Neuro-31308,
  year={2015},
  doi={10.1038/cddis.2015.121},
  title={Neuronal developmental gene and miRNA signatures induced by histone deacetylase inhibitors in human embryonic stem cells},
  volume={6},
  journal={Cell Death and Disease},
  author={Meganathan, Kesavan and Jagtap, Smita and Srinivasan, Sureshkumar Perumal and Wagh, Vilas and Hescheler, Jürgen and Hengstler, Jan and Leist, Marcel and Sachinidis, Agapios},
  note={Article Number: e1756}
}
RDF
<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/server/rdf/resource/123456789/31308">
    <dc:contributor>Wagh, Vilas</dc:contributor>
    <dcterms:issued>2015</dcterms:issued>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-06-29T09:38:00Z</dcterms:available>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/31308"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/31308/1/Meganathan_0-291341.pdf"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:language>eng</dc:language>
    <dc:contributor>Leist, Marcel</dc:contributor>
    <dc:creator>Jagtap, Smita</dc:creator>
    <dc:creator>Sachinidis, Agapios</dc:creator>
    <dcterms:abstract xml:lang="eng">Human embryonic stem cells (hESCs) may be applied to develop human-relevant sensitive in vitro test systems for monitoring developmental toxicants. The aim of this study was to identify potential developmental toxicity mechanisms of the histone deacetylase inhibitors (HDAC) valproic acid (VPA), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) relevant to the in vivo condition using a hESC model in combination with specific differentiation protocols and genome-wide gene expression and microRNA profiling. Analysis of the gene expression data showed that VPA repressed neural tube and dorsal forebrain (OTX2, ISL1, EMX2 and SOX10)-related transcripts. In addition, VPA upregulates axonogenesis and ventral forebrain-associated genes, such as SLIT1, SEMA3A, DLX2/4 and GAD2. HDACi-induced expression of miR-378 and knockdown of miR-378 increases the expression of OTX2 and EMX2, which supports our hypothesis that HDACi targets forebrain markers through miR-378. In conclusion, multilineage differentiation in vitro test system is very sensitive for monitoring molecular activities relevant to in vivo neuronal developmental toxicity. Moreover, miR-378 seems to repress the expression of the OTX2 and EMX2 and therefore could be a regulator of the development of neural tube and dorsal forebrain neurons.</dcterms:abstract>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:contributor>Hengstler, Jan</dc:contributor>
    <dc:creator>Meganathan, Kesavan</dc:creator>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/31308/1/Meganathan_0-291341.pdf"/>
    <dc:contributor>Sachinidis, Agapios</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-06-29T09:38:00Z</dc:date>
    <dc:contributor>Hescheler, Jürgen</dc:contributor>
    <dc:creator>Wagh, Vilas</dc:creator>
    <dc:contributor>Srinivasan, Sureshkumar Perumal</dc:contributor>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dc:creator>Hengstler, Jan</dc:creator>
    <dc:creator>Leist, Marcel</dc:creator>
    <dcterms:title>Neuronal developmental gene and miRNA signatures induced by histone deacetylase inhibitors in human embryonic stem cells</dcterms:title>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dc:contributor>Meganathan, Kesavan</dc:contributor>
    <dc:contributor>Jagtap, Smita</dc:contributor>
    <dc:creator>Hescheler, Jürgen</dc:creator>
    <dc:creator>Srinivasan, Sureshkumar Perumal</dc:creator>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Diese Publikation teilen