title: RNAi screen reveals potentially novel roles of cytokines in myoblast differentiation.
abstract: Cytokines are cell-secreted signaling molecules that modulate various cellular functions, with the best-characterized roles in immune responses. The expression of numerous cytokines in skeletal muscle tissues and muscle cells has been reported, but their function in skeletal myogenesis, the formation of skeletal muscle, has been largely underexplored. To systematically examine the potential roles of cytokines in skeletal myogenesis, we undertook an RNAi screen of 134 mouse cytokine genes for their involvement in the differentiation of C2C12 myoblasts. Our results have uncovered 29 cytokines as strong candidates for novel myogenic regulators, potentially conferring positive and negative regulation at distinct stages of myogenesis. These candidates represent a diverse collection of cytokine families, including interleukins, TNF-related factors, and chemokines. Our findings suggest the fundamental importance of cytokines in the cell-autonomous regulation of myoblast differentiation, and may facilitate future identification of novel therapeutic targets for improving muscle regeneration and growth in health and diseases.
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Yejing
authors.initials: Y
authors.lastname: Ge
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Waldemer
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Nalluri
authors.forename: Paul D
authors.initials: PD
authors.lastname: Nuzzi
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D007378:Interleukins / Q000235:genetics; D051379:Mice; D024510:Muscle Development / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D048069:Tumor Necrosis Factors / Q000235:genetics
chemical_list: D018925:Chemokines; D016207:Cytokines; D007378:Interleukins; D048069:Tumor Necrosis Factors