Down-regulation of myogenin can reverse terminal muscle cell differentiation.

Certain higher vertebrates developed the ability to reverse muscle cell differentiation (dedifferentiation) as an additional mechanism to regenerate muscle. Mammals, on the other hand, show limited ability to reverse muscle cell differentiation. Myogenic Regulatory Factors (MRFs), MyoD, myogenin, My...

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Main Authors: Nikolaos P Mastroyiannopoulos, Paschalis Nicolaou, Mustafa Anayasa, James B Uney, Leonidas A Phylactou
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3250496?pdf=render
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author Nikolaos P Mastroyiannopoulos
Paschalis Nicolaou
Mustafa Anayasa
James B Uney
Leonidas A Phylactou
author_facet Nikolaos P Mastroyiannopoulos
Paschalis Nicolaou
Mustafa Anayasa
James B Uney
Leonidas A Phylactou
author_sort Nikolaos P Mastroyiannopoulos
collection DOAJ
description Certain higher vertebrates developed the ability to reverse muscle cell differentiation (dedifferentiation) as an additional mechanism to regenerate muscle. Mammals, on the other hand, show limited ability to reverse muscle cell differentiation. Myogenic Regulatory Factors (MRFs), MyoD, myogenin, Myf5 and Myf6 are basic-helix-loop-helix (bHLH) transcription factors essential towards the regulation of myogenesis.Our current interest is to investigate whether down-regulation of MRFs in terminally differentiated mouse myotubes can induce reversal of muscle cell differentiation. Results from this work showed that reduction of myogenin levels in terminally differentiated mouse myotubes can reverse their differentiation state. Down-regulation of myogenin in terminally differentiated mouse myotubes induces cellular cleavage into mononucleated cells and cell cycle re-entry, as shown by re-initiation of DNA synthesis and increased cyclin D1 and cyclin E2 levels. Finally, we provide evidence that down-regulation of myogenin causes cell cycle re-entry (via down-regulation of MyoD) and cellularisation through separate pathways. These data reveal the important role of myogenin in maintaining terminal muscle cell differentiation and point to a novel mechanism by which muscle cells could be re-activated through its down-regulation.
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spelling doaj.art-6c435bd58b7446318478f5e3b4fe32e72022-12-22T02:08:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0171e2989610.1371/journal.pone.0029896Down-regulation of myogenin can reverse terminal muscle cell differentiation.Nikolaos P MastroyiannopoulosPaschalis NicolaouMustafa AnayasaJames B UneyLeonidas A PhylactouCertain higher vertebrates developed the ability to reverse muscle cell differentiation (dedifferentiation) as an additional mechanism to regenerate muscle. Mammals, on the other hand, show limited ability to reverse muscle cell differentiation. Myogenic Regulatory Factors (MRFs), MyoD, myogenin, Myf5 and Myf6 are basic-helix-loop-helix (bHLH) transcription factors essential towards the regulation of myogenesis.Our current interest is to investigate whether down-regulation of MRFs in terminally differentiated mouse myotubes can induce reversal of muscle cell differentiation. Results from this work showed that reduction of myogenin levels in terminally differentiated mouse myotubes can reverse their differentiation state. Down-regulation of myogenin in terminally differentiated mouse myotubes induces cellular cleavage into mononucleated cells and cell cycle re-entry, as shown by re-initiation of DNA synthesis and increased cyclin D1 and cyclin E2 levels. Finally, we provide evidence that down-regulation of myogenin causes cell cycle re-entry (via down-regulation of MyoD) and cellularisation through separate pathways. These data reveal the important role of myogenin in maintaining terminal muscle cell differentiation and point to a novel mechanism by which muscle cells could be re-activated through its down-regulation.http://europepmc.org/articles/PMC3250496?pdf=render
spellingShingle Nikolaos P Mastroyiannopoulos
Paschalis Nicolaou
Mustafa Anayasa
James B Uney
Leonidas A Phylactou
Down-regulation of myogenin can reverse terminal muscle cell differentiation.
PLoS ONE
title Down-regulation of myogenin can reverse terminal muscle cell differentiation.
title_full Down-regulation of myogenin can reverse terminal muscle cell differentiation.
title_fullStr Down-regulation of myogenin can reverse terminal muscle cell differentiation.
title_full_unstemmed Down-regulation of myogenin can reverse terminal muscle cell differentiation.
title_short Down-regulation of myogenin can reverse terminal muscle cell differentiation.
title_sort down regulation of myogenin can reverse terminal muscle cell differentiation
url http://europepmc.org/articles/PMC3250496?pdf=render
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