title: G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy.
abstract: Duchenne muscular dystrophy (DMD) is a chronic and life-threatening disease that is initially supported by muscle regeneration but eventually shows satellite cell exhaustion and muscular dysfunction. The life-long maintenance of skeletal muscle homoeostasis requires the satellite stem cell pool to be preserved. Asymmetric cell division plays a pivotal role in the maintenance of the satellite cell pool. Here we show that granulocyte colony-stimulating factor receptor (G-CSFR) is asymmetrically expressed in activated satellite cells. G-CSF positively affects the satellite cell population during multiple stages of differentiation in ex vivo cultured fibres. G-CSF could be important in developing an effective therapy for DMD based on its potential to modulate the supply of multiple stages of regenerated myocytes. This study shows that the G-CSF-G-CSFR axis is fundamentally important for long-term muscle regeneration, functional maintenance and lifespan extension in mouse models of DMD with varying severities.
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Nozomi
authors: N
authors: Hayashiji
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Shinsuke
authors: S
authors: Yuasa
authors: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
authors: Yuko
authors: Y
authors: Miyagoe-Suzuki
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Mie
authors: M
authors: Hara
authors: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
authors: Naoki
authors: N
authors: Ito
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Hisayuki
authors: H
authors: Hashimoto
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Dai
authors: D
authors: Kusumoto
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Tomohisa
authors: T
authors: Seki
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Shugo
authors: S
authors: Tohyama
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Masaki
authors: M
authors: Kodaira
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Akira
authors: A
authors: Kunitomi
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Shin
authors: S
authors: Kashimura
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Makoto
authors: M
authors: Takei
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Yuki
authors: Y
authors: Saito
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Shinichiro
authors: S
authors: Okata
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Toru
authors: T
authors: Egashira
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Jin
authors: J
authors: Endo
authors: Department of Comparative and Experimental Medicine, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
authors: Toshikuni
authors: T
authors: Sasaoka
authors: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
authors: Shin'ichi
authors: S
authors: Takeda
authors: Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Keiichi
authors: http://orcid.org/0000-0003-1413-0482
authors: K
authors: Fukuda
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008136:Longevity / Q000187:drug effects; D051379:Mice; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics*; D012038:Regeneration / Q000187:drug effects* / Q000235:genetics; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor