Publikation:

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

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2015

Autor:innen

Meganathan, Kesavan
Jagtap, Smita
Srinivasan, Sureshkumar Perumal
Wagh, Vilas
Hescheler, Jürgen
Hengstler, Jan
Sachinidis, Agapios

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http://nbn-resolving.de/urn:nbn:de:bsz:352-0-291341
DOI (zitierfähiger Link)
https://doi.org/10.1038/cddis.2015.121
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CC BY 4.0

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Open Access-Veröffentlichung
Open Access Gold

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Biologie: Publikationen
Core Facility der Universität Konstanz

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Cell Death and Disease. 2015, 6, e1756. eISSN 2041-4889. Available under: doi: 10.1038/cddis.2015.121

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

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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}
}
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