TY - JOUR TI - Tension-driven multi-scale self-organisation in human iPSC-derived muscle fibers AU - Mao, Qiyan AU - Acharya, Achyuth AU - Rodríguez-delaRosa, Alejandra AU - Marchiano, Fabio AU - Dehapiot, Benoit AU - Al Tanoury, Ziad AU - Rao, Jyoti AU - Díaz-Cuadros, Margarete AU - Mansur, Arian AU - Wagner, Erica AU - Chardes, Claire AU - Gupta, Vandana AU - Lenne, Pierre-François AU - Habermann, Bianca H AU - Theodoly, Olivier AU - Pourquié, Olivier AU - Schnorrer, Frank A2 - Tanentzapf, Guy A2 - Stainier, Didier YR VL - 11 PY - 2022 DA - 2022/08/03 SP - e76649 C1 - eLife 2022;11:e76649 DO - 10.7554/eLife.76649 UR - https://doi.org/10.7554/eLife.76649 AB - Human muscle is a hierarchically organised tissue with its contractile cells called myofibers packed into large myofiber bundles. Each myofiber contains periodic myofibrils built by hundreds of contractile sarcomeres that generate large mechanical forces. To better understand the mechanisms that coordinate human muscle morphogenesis from tissue to molecular scales, we adopted a simple in vitro system using induced pluripotent stem cell-derived human myogenic precursors. When grown on an unrestricted two-dimensional substrate, developing myofibers spontaneously align and self-organise into higher-order myofiber bundles, which grow and consolidate to stable sizes. Following a transcriptional boost of sarcomeric components, myofibrils assemble into chains of periodic sarcomeres that emerge across the entire myofiber. More efficient myofiber bundling accelerates the speed of sarcomerogenesis suggesting that tension generated by bundling promotes sarcomerogenesis. We tested this hypothesis by directly probing tension and found that tension build-up precedes sarcomere assembly and increases within each assembling myofibril. Furthermore, we found that myofiber ends stably attach to other myofibers using integrin-based attachments and thus myofiber bundling coincides with stable myofiber bundle attachment in vitro. A failure in stable myofiber attachment results in a collapse of the myofibrils. Overall, our results strongly suggest that mechanical tension across sarcomeric components as well as between differentiating myofibers is key to coordinate the multi-scale self-organisation of muscle morphogenesis. KW - muscle KW - sarcomere KW - self-organisation KW - mechanical tension KW - human induced pluripotent stem cells KW - myofibril JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -