title: A Pitx2-MicroRNA Pathway Modulates Cell Proliferation in Myoblasts and Skeletal-Muscle Satellite Cells and Promotes Their Commitment to a Myogenic Cell Fate.
abstract: The acquisition of a proliferating-cell status from a quiescent state as well as the shift between proliferation and differentiation are key developmental steps in skeletal-muscle stem cells (satellite cells) to provide proper muscle regeneration. However, how satellite cell proliferation is regulated is not fully understood. Here, we report that the c-isoform of the transcription factor Pitx2 increases cell proliferation in myoblasts by downregulating microRNA 15b (miR-15b), miR-23b, miR-106b, and miR-503. This Pitx2c-microRNA (miRNA) pathway also regulates cell proliferation in early-activated satellite cells, enhancing Myf5(+) satellite cells and thereby promoting their commitment to a myogenic cell fate. This study reveals unknown functions of several miRNAs in myoblast and satellite cell behavior and thus may have future applications in regenerative medicine.
authors.affiliation: Cardiac and Skeletal Myogenesis Group, Department of Experimental Biology, University of Jaén, Jaén, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Lozano-Velasco
authors.affiliation: Cardiac and Skeletal Myogenesis Group, Department of Experimental Biology, University of Jaén, Jaén, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vallejo
authors.affiliation: Cardiac and Skeletal Myogenesis Group, Department of Experimental Biology, University of Jaén, Jaén, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteban
authors.affiliation: Cardiac and Skeletal Myogenesis Group, Department of Experimental Biology, University of Jaén, Jaén, Spain.
authors.forename: Chris
authors.initials: C
authors.lastname: Doherty
authors.affiliation: Cardiac and Skeletal Myogenesis Group, Department of Experimental Biology, University of Jaén, Jaén, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernández-Torres
authors.affiliation: Cardiac and Skeletal Myogenesis Group, Department of Experimental Biology, University of Jaén, Jaén, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Franco
authors.affiliation: Cardiac and Skeletal Myogenesis Group, Department of Experimental Biology, University of Jaén, Jaén, Spain aaranega@ujaen.es.
authors.forename: Amelia Eva
authors.initials: AE
authors.lastname: Aránega
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D024510:Muscle Development / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000166:cytology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C543896:Mirn106 microRNA, mouse; C570833:Mirn15 microRNA, mouse; C534062:Mirn23b microRNA, mouse; C556275:Mirn503 microRNA, mouse