title: Intramuscular adipogenesis is inhibited by myo-endothelial progenitors with functioning Bmpr1a signalling.
abstract: Developing human muscle contains inter-myofibre progenitors expressing Bmp-receptor 1a (Bmpr1a) and Myf5 that respond to stimulation with Bmp4. Here we ablate Bmpr1a in Myf5- and MyoD-expressing cells in vivo. Mutant mice reveal increased intramuscular fat and reduced myofibre size in selected muscles, or following muscle injury. Myo-endothelial progenitors are the most affected cell type: clonal studies demonstrate that ablation of Bmpr1a in myo-endothelial cells results in decreased myogenic activity, while adipogenic differentiation is significantly increased. Downstream phospho-Smad 1, 5, 8 signalling is also severely decreased in mutant myo-endothelial cells. Lineage tracing of endothelial cells using VE-cadherin(Cre) driver failed to reveal a significant contribution of these cells to developing or injured skeletal muscle. Thus, myo-endothelial progenitors with functioning Bmpr1a signalling demonstrate myogenic potential, but their main function in vivo is to inhibit intramuscular adipogenesis, both through a cell-autonomous and a cell-cell interaction mechanism.
authors.affiliation: Division of Genetics, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.affiliation: 1] Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, Massachusetts 02115, USA [2].
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Schulz
authors.affiliation: 1] Division of Genetics, Boston Children's Hospital, Boston, Massachusetts 02115, USA [2].
authors.forename: Ariane
authors.initials: A
authors.lastname: Beauvais
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, Massachusetts 02115, USA.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Tseng
authors.affiliation: Division of Genetics, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Gussoni
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D015703:Antigens, CD; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics*; D015820:Cadherins; D042783:Endothelial Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D051904:Smad8 Protein / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D052005:Bone Morphogenetic Protein Receptors, Type I; D015820:Cadherins; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D051898:Smad1 Protein; D051902:Smad5 Protein; D051904:Smad8 Protein; D000099152:Cadherin 5; C497418:Myf5 protein, mouse; C057363:MyoD1 myogenic differentiation protein; C497401:Smad1 protein, mouse; C497798:Smad5 protein, mouse; C491621:Smad9 protein, mouse; C498212:Bmpr1a protein, mouse