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miR669a and miR669q prevent skeletal muscle differentiation in postnatal cardiac progenitors

Stefania Crippa and Marco Cassano and Graziella Messina and Daniela Galli and Beatriz G. Galvez and Tomaz Curk and Claudia Altomare and Flavio Ronzoni and Jaan Toelen and Rik Gijsbers and Zeger Debyser and Stefan Janssens and Blaz Zupan and Antonio Zaza and Giulio Cossu and Maurilio Sampaolesi (2011) miR669a and miR669q prevent skeletal muscle differentiation in postnatal cardiac progenitors. J Cell Biol, 193 . pp. 1197-1212.

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Postnatal heart stem and progenitor cells are a potential therapeutic tool for cardiomyopathies, but little is known about the mechanisms that control cardiac differentiation. Recent work has highlighted an important role for microribonucleic acids (miRNAs) as regulators of cardiac and skeletal myogenesis. In this paper, we isolated cardiac progenitors from neonatal β-sarcoglycan (Sgcb)-null mouse hearts affected by dilated cardiomyopathy. Unexpectedly, Sgcb-null cardiac progenitors spontaneously differentiated into skeletal muscle fibers both in vitro and when transplanted into regenerating muscles or infarcted hearts. Differentiation potential correlated with the absence of expression of a novel miRNA, miR669q, and with down-regulation of miR669a. Other miRNAs are known to promote myogenesis, but only miR669a and miR669q act upstream of myogenic regulatory factors to prevent myogenesis by directly targeting the MyoD 3' untranslated region. This finding reveals an added level of complexity in the mechanism of the fate choice of mesoderm progenitors and suggests that using endogenous cardiac stem cells therapeutically will require specially tailored procedures for certain genetic diseases.

Item Type: Article
Keywords: skeletal muscle differentiation, cardiomyopathies, miRNA
Related URLs:
http://www.cobiss.si/scripts/cobiss?command=search&base=50070&select=(id=8455252)Alternative location
Institution: University of Ljubljana
Department: Faculty of Computer and Information Science
Divisions: Faculty of Computer and Information Science > Bioinformatics Laboratory
Item ID: 1475
Date Deposited: 22 Jul 2011 12:58
Last Modified: 02 Dec 2013 14:33
URI: http://eprints.fri.uni-lj.si/id/eprint/1475

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