title: Myf5 haploinsufficiency reveals distinct cell fate potentials for adult skeletal muscle stem cells.
abstract: Skeletal muscle stem cell fate in adult mice is regulated by crucial transcription factors, including the determination genes Myf5 and Myod. The precise role of Myf5 in regulating quiescent muscle stem cells has remained elusive. Here we show that most, but not all, quiescent satellite cells express Myf5 protein, but at varying levels, and that resident Myf5 heterozygous muscle stem cells are more primed for myogenic commitment compared with wild-type satellite cells. Paradoxically however, heterotypic transplantation of Myf5 heterozygous cells into regenerating muscles results in higher self-renewal capacity compared with wild-type stem cells, whereas myofibre regenerative capacity is not altered. By contrast, Pax7 haploinsufficiency does not show major modifications by transcriptome analysis. These observations provide a mechanism linking Myf5 levels to muscle stem cell heterogeneity and fate by exposing two distinct and opposing phenotypes associated with Myf5 haploinsufficiency. These findings have important implications for how stem cell fates can be modulated by crucial transcription factors while generating a pool of responsive heterogeneous cells.
authors.affiliation: Stem Cells and Development, Department of Developmental Biology, Institut Pasteur, CNRS URA 2578, Paris, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gayraud-Morel
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chrétien
authors.forename: Aurélie
authors.initials: A
authors.lastname: Jory
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Sambasivan
authors.forename: Elisa
authors.initials: E
authors.lastname: Negroni
authors.forename: Patricia
authors.initials: P
authors.lastname: Flamant
authors.forename: Guillaume
authors.initials: G
authors.lastname: Soubigou
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Coppée
authors.forename: James
authors.initials: J
authors.lastname: Di Santo
authors.forename: Ana
authors.initials: A
authors.lastname: Cumano
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.forename: Shahragim
authors.initials: S
authors.lastname: Tajbakhsh
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D019070:Cell Lineage; D057895:Haploinsufficiency / Q000235:genetics*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000378:metabolism*; D051787:Myogenic Regulatory Factor 5 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D010641:Phenotype
chemical_list: C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse