title: Embryonic founders of adult muscle stem cells are primed by the determination gene Mrf4.
abstract: Skeletal muscle satellite cells play a critical role during muscle growth, homoeostasis and regeneration. Selective induction of the muscle determination genes Myf5, Myod and Mrf4 during prenatal development can potentially impact on the reported functional heterogeneity of adult satellite cells. Accordingly, expression of Myf5 was reported to diminish the self-renewal potential of the majority of satellite cells. In contrast, virtually all adult satellite cells showed antecedence of Myod activity. Here we examine the priming of myogenic cells by Mrf4 throughout development. Using a Cre-lox based genetic strategy and novel highly sensitive Pax7 reporter alleles compared to the ubiquitous Rosa26-based reporters, we show that all adult satellite cells, independently of their anatomical location or embryonic origin, have been primed for Mrf4 expression. Given that Mrf4Cre and Mrf4nlacZ are active exclusively in progenitors during embryogenesis, whereas later expression is restricted to differentiated myogenic cells, our findings suggest that adult satellite cells emerge from embryonic founder cells in which the Mrf4 locus was activated. Therefore, this level of myogenic priming by induction of Mrf4, does not compromise the potential of the founder cells to assume an upstream muscle stem cell state. We propose that embryonic myogenic cells and the majority of adult muscle stem cells form a lineage continuum.
authors.affiliation: Institut Pasteur, Stem Cells & Development, CNRS URA 2578, 25 rue du Dr. Roux, 75724, Paris Cedex 15, France.
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Sambasivan
authors.forename: Glenda
authors.initials: G
authors.lastname: Comai
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Roux
authors.forename: Danielle
authors.initials: D
authors.lastname: Gomès
authors.forename: Julie
authors.initials: J
authors.lastname: Konge
authors.forename: Gérard
authors.initials: G
authors.lastname: Dumas
authors.forename: Clémire
authors.initials: C
authors.lastname: Cimper
authors.forename: Shahragim
authors.initials: S
authors.lastname: Tajbakhsh
mesh_terms: D000483:Alleles; D000818:Animals; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D024510:Muscle Development; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D051763:PAX7 Transcription Factor / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; C063403:myogenic factor 6; D049452:Green Fluorescent Proteins
keywords: Lineage; Mrf4; Myf5; Pax7; Reporter mice; Skeletal muscle stem cells