京都府立医科大学大学院医学研究科  免疫学(松田研究室)
Department of Immunology, Kyoto Prefectural University of Medicine

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筋芽細胞のダイレクト・リプログラミングと筋管形成
Direct reprogramming of functional myoblasts that are capable of forming multinuclear myotube

筋芽細胞のダイレクト・リプログラミングと筋管形成

The skeletal muscle consists of contractile myofibers and plays essential roles for maintenance of body posture, movement, and metabolic regulation. During the development and regeneration of the skeletal muscle tissue, the myoblasts fuse into multinucleated myotubes that subsequently form myofibers. Transplantation of myoblasts may make possible a novel regenerative therapy against defects or dysfunction of the skeletal muscle. It is reported that rodent fibroblasts are converted into myoblast-like cells and fuse to form syncytium after forced expression of exogenous MyoD1 that is a key transcription factor for myoblast differentiation. But human fibroblasts are less efficiently converted into myoblasts and rarely fused by MyoD1 alone. Here we found that transduction of L-myc gene in combination with MyoD1 gene induced myoblast-like phenotypes in human fibroblasts more strongly than MyoD1 gene alone. The rate of conversion was approximately 90%. The directly converted myoblasts (dMBs) underwent fusion in an ERK5 pathway-dependent manner. The dMBs also formed myofiber-like structure in vivo after an inoculation into mice at the subcutaneous tissue. The present results strongly suggest that the combination of L-myc plus MyoD1 may promote direct conversion of human fibroblasts into functional myoblasts that could potentially be used for regenerative therapy for muscle diseases and congenital muscle defects. (Wakao J. et al, BBRC.).

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