発生研セミナー
講演者： 朝倉 淳 (Stem Cell Institute, Muscular Dystrophy Center, University of Minnesota Medical School)
演題: Vascular niche and reprogramming for skeletal muscle stem cell
日時： 2019年12月9日（月） 12:00-13:00
会場： 発生医学研究所1階 カンファレンス室
Abstract:
Muscle satellite cells are a stem cell population responsible for skeletal muscle growth, repairand regeneration. Maintenance of the balance between satellite cell differentiation and self-renewal is required for muscle homeostasis. By utilizing fluorescent reporter mice, muscle tissue clearing and confocal/two-photon microscopy to investigate the specific niche for muscle satellite cells in 3-dimensions, we recently reported that the juxtavascular niche of satellite cells for stem cell maintenance via VEGF and Notch pathways (Verma, et al. Cell Stem Cell, 2018). Increased vascular density could induce increased number of satellite cells, which leads to a beneficial effect on Duchenne muscular dystrophy (DMD) model mice. Based on these results, we recently generated anti-FLT1 monoclonal antibodies, which blocked binding of VEGF and FLT1 (VEGFR1), a decoly receptor for VEGF. The histological and functional improvement of dystrophic muscle by FLT1-blockade provides a novel pharmacological strategy for the potential treatment of DMD (Verma et al., PLoS Genet, 2019, in press). We also identified that ASCL4, a basic-Helix-Loop-Helix (bHLH) transcription factor, possesses an ability to induce myogenic program in pluripotent embryonic stem (ES) cells via binding to MyoD enhancer region, indicating that ASCL4 acts as a myogenic transcription factor during muscle development, and that ASCL4-mediated myogenic conversion of pluripotent stem cells will be a new therapy for DMD.
References:
M. Verma, Y. Asakura, B. S. R. Murakonda, T. Pengo, C. Latroche, B. Chazaud, L. K. McLoon, A. Asakura. Muscle Satellite cell cross-talk with a vascular niche maintains quiescence via VEGF and Notch signaling. Cell Stem Cell. 23:530-543 (2018)
M. Verma, Y. Shimizu-Motohashi, Y. Asakura, J. P. Ennen, J. Boscof, Z. Zhou, G.-H. Fong, S. Josiah, D. Keefe, A. Asakura. Inhibition of FLT1 ameliorates muscular dystrophy phenotype by increased vasculature in a mouse model of Duchenne muscular dystrophy. PLoS Genet (2019) In Press
担当分野： 筋発生再生分野 小野（内線番号）6601
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