Tension-driven multi-scale self-organisation in human iPSC-derived muscle fibers
Year: 2022
Type: article
Abstract: 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.
Source: eLife
DOI: 10.7554/elife.76649
Authors: Qiyan Mao, Achyuth Acharya, Alejandra Rodríguez-delaRosa, Fabio Marchiano, Benoit Dehapiot, Ziad Al Tanoury, Jyoti Rao, Margarete Díaz-Cuadros, Arian Mansur, Erica Wagner, Claire Chardes, Vandana A. Gupta, Pierre-François Lenne, Bianca H. Habermann, Olivier Theodoly, Olivier Pourquie, Frank Schnorrer
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,075
Funders: Harvard University, Aix-Marseille Université, National Academies of Sciences, Engineering, and Medicine, European Commission, Human Frontier Science Program, Agence Nationale de la Recherche, Technische Universität Dresden, Centre National de la Recherche Scientifique, Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona, National Institutes of Health, European Research Council, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1255325603, CenTuri : Centre Turing des Systèmes vivants, INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE, G1742243815, Systematic functional analysis of mitochondrial dynamics in healthy young, aged and sarcopenic muscle, G2441619162, Elucidating the Role of Metabolism in Regulating the Vertebrate Segmentation Clock, G2553460746, G262592543, G381665449, G3868750453, G434337789, G4586079565, G4656594441, G4866930200, G4950536974, G5132640529, G572841159, G6004110409, G7011901419, G7240651115, G7685134749, G7731791180, G782245399, In vivo quantification and manipulation of mechanical forces across muscle attachment sites and sarcomeric proteins during muscle morphogenesis, G7905814814, G8220984285
OpenAlex ID: W4289550042