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Title: miR669a and miR669q prevent skeletal muscle differentiation in postnatal cardiac progenitors
Authors: Crippa, Stefania
Cassano, Marco
Messina, Graziella
Galli, Daniela
Galvez, Beatriz G
Curk, Tomaz
Altomare, Claudia
Ronzoni, Flavio
Toelen, Jaan
Gijsbers, Rik
Debyser, Zeger
Janssens, Stefan
Zupan, Blaz
Zaza, Antonio
Cossu, Giulio
Sampaolesi, Maurilio # ×
Issue Date: Jun-2011
Publisher: Rockefeller Institute Press
Series Title: Journal of Cell Biology vol:193 issue:7 pages:1197-1212
Abstract: 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.
URI: 
ISSN: 0021-9525
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
Interdepartemental Stem Cell Institute (-)
Cardiology
× corresponding author
# (joint) last author

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