Intrinsic phenotypic diversity of embryonic and fetal myoblasts is revealed by genome-wide gene expression analysis on purified cells.
Skeletal muscle development occurs asynchronously and it has been proposed to be dependent upon the generation of temporally distinct populations of myogenic cells. This long-held hypothesis has not been tested directly due to the inability to isolate and analyze purified populations of myoblasts derived from specific stages of prenatal development. Using a mouse strain with the GFP reporter gene targeted into the Myf5 locus, a cell-sorting method was developed for isolating embryonic and fetal myoblasts. The two types of myoblasts show an intrinsic difference in fusion ability, proliferation, differentiation and response to TGFbeta, TPA and BMP-4 in vitro. Microarray and quantitative PCR were used to identify differentially expressed genes both before and after differentiation, thus allowing a precise phenotypic analysis of the two populations. Embryonic and fetal myoblasts differ in the expression of a number of transcription factors and surface molecules, which may control different developmental programs. For example, only embryonic myoblasts express a Hox code along the antero-posterior axis, indicating that they possess direct positional information. Taken together, the data presented here demonstrate that embryonic and fetal myoblasts represent intrinsically different myogenic lineages and provide important information for the understanding of the molecular mechanisms governing skeletal muscle development.
Biressi
Stefano
S
Stem Cell Research Institute, Dibit, H. San Raffaele, via Olgettina 58, 20132 Milan, Italy.
Tagliafico
Enrico
E
Lamorte
Giuseppe
G
Monteverde
Stefania
S
Tenedini
Elena
E
Roncaglia
Enrica
E
Ferrari
Sergio
S
Ferrari
Stefano
S
Cusella-De Angelis
Maria Gabriella
MG
Tajbakhsh
Shahragim
S
Cossu
Giulio
G
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005333:Fetus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology* / Q000196:embryology; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D013755:Tetradecanoylphorbol Acetate