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Biomechanical Origins of Muscle Stem Cell Signal Transduction

机译:肌肉干细胞信号转导的生物力学起源

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Skeletal muscle, the most abundant and widespread tissue in the human body, contracts upon receiving electrochemical signals from the nervous system to support essential functions such as thermoregulation, limb movement, blinking, swallowing and breathing. Reconstruction of adult muscle tissue relies on a pool of mononucleate, resident muscle stem cells, known as "satellite cells", expressing the paired-box transcription factor Pax7 necessary for their specification during embryonic development and long-term maintenance during adult life. Satellite cells are located around the myofibres in a niche at the interface of the basal lamina and the host fibre plasma membrane (i.e., sarcolemma), at a very low frequency. Upon damage to the myofibres, quiescent satellite cells are activated and give rise to a population of transient amplifying myogenic progenitor cells, which eventually exit the cell cycle permanently and fuse to form new myofibres and regenerate the tissue. A subpopulation of satellite cells self-renew and repopulate the niche, poised to respond to future demands. Harnessing the potential of satellite cells relies on a complete understanding of the molecular mechanisms guiding their regulation in vivo. Over the past several decades, studies revealed many signal transduction pathways responsible for satellite cell fate decisions, but the niche cues driving the activation and silencing of these pathways are less clear. Here we explore the scintillating possibility that considering the dynamic changes in the biophysical properties of the skeletal muscle, namely stiffness, and the stretch and shear forces to which a myofibre can be subjected to may provide missing information necessary to gain a full understanding of satellite cell niche regulation. (C) 2015 Elsevier Ltd. All rights reserved.
机译:骨骼肌是人体中最丰富,分布最广泛的组织,它在从神经系统接收电化学信号后收缩,以支持基本功能,例如体温调节,四肢运动,眨眼,吞咽和呼吸。成年肌肉组织的重建依赖于称为“卫星细胞”的单核常驻肌肉干细胞库,表达成对盒转录因子Pax7,这是它们在胚胎发育和成年后长期维持过程中所必需的。卫星细胞以非常低的频率位于基底膜和宿主纤维质膜(即肉瘤)的界面上的壁iche中的肌纤维周围。肌纤维受损后,静止的卫星细胞被激活,并产生大量瞬时扩增的成肌祖细胞,这些细胞最终永久退出细胞周期并融合形成新的肌纤维并再生组织。卫星细胞的亚群会自我更新并重新填充利基,随时准备应对未来的需求。利用卫星细胞的潜力取决于对指导其体内调节的分子机制的全面理解。在过去的几十年中,研究表明,许多信号转导通路决定着卫星细胞的命运,但驱动这些通路激活和沉默的利基线索尚不清楚。在这里,我们探讨了闪烁的可能性,即考虑骨骼肌的生物物理特性的动态变化(即刚度)以及肌原纤维可以承受的拉伸和剪切力可能会提供缺失的信息,从而无法充分了解卫星细胞利基监管。 (C)2015 Elsevier Ltd.保留所有权利。

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