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FGF6 mediated expansion of a resident subset of cells with SP phenotype in the C2C12 myogenic line.

Israeli, D; Benchaouir, R; Ziaei, S; Rameau, P; Gruszczynski, C; Peltekian, E; Danos, O; (2004) FGF6 mediated expansion of a resident subset of cells with SP phenotype in the C2C12 myogenic line. J Cell Physiol , 201 (3) pp. 409-419. 10.1002/jcp.20088.

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Abstract

Fibroblast growth factor 6 (FGF6) is selectively expressed during muscle development and regeneration. We examined its effect on muscle precursor cells (mpc) by forcing stable FGF6 expression in C2C12 cells in vitro. FGF6 produced in genetically engineered mpc was active, inducing strong morphological changes, altering cell adhesion and compromising their ability to differentiate into myotubes. Expression of MyoD and myogenin, but not of Myf5, was abrogated in FGF6 engineered mpc. These effects were reversed by FGF inhibitors. Ectopic expression of MyoD also restored fiber formation indicating that FGF6 interferes with the myogenic differentiation pathway upstream of MyoD. We also report that in the presence of FGF6, the minor (0.5-2%) subpopulation of cells actively excluding Hoechst 33342 in a verapamil-dependent manner (SP phenotype) was increased to 15-20% and the expression of the mdr1a gene (but not mdr1b) was upregulated by 400-fold. Our data establish a previously undescribed link between FGF6--a muscle specific growth factor--and a multidrug resistance gene expressed in stem cells, and suggest a role for FGF6 in the maintenance of a reserve pool of progenitor cells in the skeletal muscle.

Type: Article
Title: FGF6 mediated expansion of a resident subset of cells with SP phenotype in the C2C12 myogenic line.
Location: United States
DOI: 10.1002/jcp.20088
Keywords: ATP Binding Cassette Transporter, Subfamily B, ATP-Binding Cassette Transporters, Animals, Cell Cycle, Cell Differentiation, Cell Line, Fibroblast Growth Factor 6, Fibroblast Growth Factors, Mice, Muscle Development, Muscle, Skeletal, Phenotype, Proto-Oncogene Proteins, RNA, Messenger, Up-Regulation
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/90975
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