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Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor

Valproic acid (VPA) is a widely used antiepileptic drug, which has recently been reported to modulate the neuronal differentiation of adipose tissue-derived stem cells (ASCs) in humans and dogs. However, controversy exists as to whether VPA really acts as an inducer of neuronal differentiation of AS...

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Autores principales: Okubo, Takumi, Hayashi, Daiki, Yaguchi, Takayuki, Fujita, Yudai, Sakaue, Motoharu, Suzuki, Takehito, Tsukamoto, Atsushi, Murayama, Ohoshi, Lynch, Jonathan, Miyazaki, Yoko, Tanaka, Kazuaki, Takizawa, Tatsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japanese Association for Laboratory Animal Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783650/
https://www.ncbi.nlm.nih.gov/pubmed/26411320
http://dx.doi.org/10.1538/expanim.15-0038
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author Okubo, Takumi
Hayashi, Daiki
Yaguchi, Takayuki
Fujita, Yudai
Sakaue, Motoharu
Suzuki, Takehito
Tsukamoto, Atsushi
Murayama, Ohoshi
Lynch, Jonathan
Miyazaki, Yoko
Tanaka, Kazuaki
Takizawa, Tatsuya
author_facet Okubo, Takumi
Hayashi, Daiki
Yaguchi, Takayuki
Fujita, Yudai
Sakaue, Motoharu
Suzuki, Takehito
Tsukamoto, Atsushi
Murayama, Ohoshi
Lynch, Jonathan
Miyazaki, Yoko
Tanaka, Kazuaki
Takizawa, Tatsuya
author_sort Okubo, Takumi
collection PubMed
description Valproic acid (VPA) is a widely used antiepileptic drug, which has recently been reported to modulate the neuronal differentiation of adipose tissue-derived stem cells (ASCs) in humans and dogs. However, controversy exists as to whether VPA really acts as an inducer of neuronal differentiation of ASCs. The present study aimed to elucidate the effect of VPA in neuronal differentiation of rat ASCs. One or three days of pretreatment with VPA (2 mM) followed by neuronal induction enhanced the ratio of immature neuron marker βIII-tubulin-positive cells in a time-dependent manner, where the majority of cells also had a positive signal for neurofilament medium polypeptide (NEFM), a mature neuron marker. RT-PCR analysis revealed increases in the mRNA expression of microtubule-associated protein 2 (MAP2) and NEFM mature neuron markers, even without neuronal induction. Three-days pretreatment of VPA increased acetylation of histone H3 of ASCs as revealed by immunofluorescence staining. Chromatin immunoprecipitation assay also showed that the status of histone acetylation at H3K9 correlated with the gene expression of TUBB3 in ASCs by VPA. These results indicate that VPA significantly promotes the differentiation of rat ASCs into neuron-like cells through acetylation of histone H3, which suggests that VPA may serve as a useful tool for producing transplantable cells for future applications in clinical treatments.
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spelling pubmed-47836502016-03-10 Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor Okubo, Takumi Hayashi, Daiki Yaguchi, Takayuki Fujita, Yudai Sakaue, Motoharu Suzuki, Takehito Tsukamoto, Atsushi Murayama, Ohoshi Lynch, Jonathan Miyazaki, Yoko Tanaka, Kazuaki Takizawa, Tatsuya Exp Anim Original Valproic acid (VPA) is a widely used antiepileptic drug, which has recently been reported to modulate the neuronal differentiation of adipose tissue-derived stem cells (ASCs) in humans and dogs. However, controversy exists as to whether VPA really acts as an inducer of neuronal differentiation of ASCs. The present study aimed to elucidate the effect of VPA in neuronal differentiation of rat ASCs. One or three days of pretreatment with VPA (2 mM) followed by neuronal induction enhanced the ratio of immature neuron marker βIII-tubulin-positive cells in a time-dependent manner, where the majority of cells also had a positive signal for neurofilament medium polypeptide (NEFM), a mature neuron marker. RT-PCR analysis revealed increases in the mRNA expression of microtubule-associated protein 2 (MAP2) and NEFM mature neuron markers, even without neuronal induction. Three-days pretreatment of VPA increased acetylation of histone H3 of ASCs as revealed by immunofluorescence staining. Chromatin immunoprecipitation assay also showed that the status of histone acetylation at H3K9 correlated with the gene expression of TUBB3 in ASCs by VPA. These results indicate that VPA significantly promotes the differentiation of rat ASCs into neuron-like cells through acetylation of histone H3, which suggests that VPA may serve as a useful tool for producing transplantable cells for future applications in clinical treatments. Japanese Association for Laboratory Animal Science 2015-09-25 2016 /pmc/articles/PMC4783650/ /pubmed/26411320 http://dx.doi.org/10.1538/expanim.15-0038 Text en ©2016 Japanese Association for Laboratory Animal Science http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License.
spellingShingle Original
Okubo, Takumi
Hayashi, Daiki
Yaguchi, Takayuki
Fujita, Yudai
Sakaue, Motoharu
Suzuki, Takehito
Tsukamoto, Atsushi
Murayama, Ohoshi
Lynch, Jonathan
Miyazaki, Yoko
Tanaka, Kazuaki
Takizawa, Tatsuya
Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor
title Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor
title_full Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor
title_fullStr Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor
title_full_unstemmed Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor
title_short Differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor
title_sort differentiation of rat adipose tissue-derived stem cells into neuron-like cells by valproic acid, a histone deacetylase inhibitor
topic Original
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783650/
https://www.ncbi.nlm.nih.gov/pubmed/26411320
http://dx.doi.org/10.1538/expanim.15-0038
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