title: miR669a and miR669q prevent skeletal muscle differentiation in postnatal cardiac progenitors.
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.
authors.affiliation: Translational Cardiomyology Laboratory, Interdepartmental Stem Cell Institute, Catholic University of Leuven, 3000 Leuven, Belgium.
authors.forename: Stefania
authors.initials: S
authors.lastname: Crippa
authors.forename: Marco
authors.initials: M
authors.lastname: Cassano
authors.forename: Graziella
authors.initials: G
authors.lastname: Messina
authors.forename: Daniela
authors.initials: D
authors.lastname: Galli
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Galvez
authors.forename: Tomaz
authors.initials: T
authors.lastname: Curk
authors.forename: Claudia
authors.initials: C
authors.lastname: Altomare
authors.forename: Flavio
authors.initials: F
authors.lastname: Ronzoni
authors.forename: Jaan
authors.initials: J
authors.lastname: Toelen
authors.forename: Rik
authors.initials: R
authors.lastname: Gijsbers
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
authors.forename: Blaz
authors.initials: B
authors.lastname: Zupan
authors.forename: Antonio
authors.initials: A
authors.lastname: Zaza
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.forename: Maurilio
authors.initials: M
authors.lastname: Sampaolesi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D015536:Down-Regulation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008957:Models, Genetic; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D012038:Regeneration; D049031:Sarcoglycans / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D049031:Sarcoglycans