Ugorets Vladimir, Mendez Paul-Lennard, Zagrebin Dmitrii, Russo Giulia, Kerkhoff Yannic, Kotsaris Georgios, Jatzlau Jerome, Stricker Sigmar, Knaus Petra
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Signal Transduction Group, 14195 Berlin, Germany.
Max Planck Institute for Molecular Genetics, IMPRS-Biology and Computation, 14195 Berlin, Germany.
iScience. 2024 Jul 31;27(9):110630. doi: 10.1016/j.isci.2024.110630. eCollection 2024 Sep 20.
Controlled myogenic differentiation is integral to the development, maintenance and repair of skeletal muscle, necessitating precise regulation of myogenic progenitors and resident stem cells. The transformation of proliferative muscle progenitors into multinuclear syncytia involves intricate cellular processes driven by cytoskeletal reorganization. While actin and microtubles have been extensively studied, we illuminate the role of septins, an essential yet still often overlooked cytoskeletal component, in myoblast architecture. Notably, Septin9 emerges as a critical regulator of myoblast differentiation during the initial commitment phase. Knock-down of Septin9 in C2C12 cells and primary mouse myoblasts accelerates the transition from proliferation to committed progenitor transcriptional programs. Furthermore, we unveil significant reorganization and downregulation of Septin9 during myogenic differentiation. Collectively, we propose that filmamentous septin structures and their orchestrated reorganization in myoblasts are part of a temporal regulatory mechanism governing the differentiation of myogenic progenitors. This study sheds light on the dynamic interplay between cytoskeletal components underlying controlled myogenic differentiation.
可控的成肌分化对于骨骼肌的发育、维持和修复至关重要，这需要对成肌祖细胞和驻留干细胞进行精确调控。增殖性肌肉祖细胞向多核合胞体的转变涉及由细胞骨架重组驱动的复杂细胞过程。虽然肌动蛋白和微管已得到广泛研究，但我们阐明了隔膜蛋白（一种重要但仍常被忽视的细胞骨架成分）在成肌细胞结构中的作用。值得注意的是，Septin9在初始承诺阶段成为成肌细胞分化的关键调节因子。在C2C12细胞和原代小鼠成肌细胞中敲低Septin9会加速从增殖到定向祖细胞转录程序的转变。此外，我们揭示了成肌分化过程中Septin9的显著重组和下调。总的来说，我们认为丝状隔膜蛋白结构及其在成肌细胞中的精心重组是控制成肌祖细胞分化的时间调节机制的一部分。这项研究揭示了可控成肌分化背后细胞骨架成分之间的动态相互作用。
