Rocheteau Pierre, Vinet Mathilde, Chretien Fabrice
Human histopathology and animal models, Institut Pasteur, 28 rue du Dr. Roux, 75724, Paris Cedex 15, France.
Results Probl Cell Differ. 2015;56:215-35. doi: 10.1007/978-3-662-44608-9_10.
The skeletal muscle of vertebrates has a huge regenerative capacity. When destroyed after different types of injury, this organ can regenerate very quickly (less than 20 days following myotoxin injection in the mouse) ad integrum and repeatedly. The cell responsible for this regeneration is the so-called satellite cell, the muscle stem cell that lies on top of the muscle fibre, a giant, multinucleated cell that contains the contractile material. When injected in the muscle, satellite cells can efficiently differentiate into contractile muscle fibres. The satellite cell shows great therapeutic potential; and its regenerative capacity has triggered particular interest in the field of muscular degeneration. In this review we will focus on one particular property of the satellite cell: its quiescence and dormancy. Indeed adult satellite cells are quiescent; they lie between the basal lamina and the basement membrane of the muscle fibre, ready to proliferate, and fuse in order to regenerate myofibers upon injury. It has recently been shown that a subpopulation of satellite cells is able to enter dormancy in human and mice cadavers. Dormancy is defined by a low metabolic state, low mobility, and a long lag before division when plated in vitro, compared to quiescent cells. This definition is also based on current knowledge about long-term hematopoietic stem cells, a subpopulation of stem cells that are described as dormant based on the same criteria (rare division and low metabolism when compared to progeny which are dividing more often). In the first part of this review, we will provide a description of satellite cells which addresses their quiescent state. We will then focus on the uneven distribution of satellite cells in the muscle and describe evidence that suggests that their dormancy differs from one muscle to the next and that one should be cautious when making generalisations regarding this cellular state. In a second part, we will discuss the transition between active dividing cells in developing animals to quiescence. This mechanism could be used or amplified in the switch from quiescence to dormancy. In a third part, we will review the signals and dynamics that actively maintain the satellite cell quiescent. The in-depth understanding of these mechanisms is key to describing how dormancy relies on quiescent state of the cells. In a fourth part, we will deal with dormancy per se: how dormant satellite cells can be obtained, their characteristics, their metabolic profile, and their molecular signature as compared to quiescent cells. Here, we will highlight one of the most important recent findings: that quiescence is a prerequisite for the entry of the satellite cell into dormancy. Since dormancy is a newly discovered phenomenon, we will review the mechanisms responsible for quiescence and activation, as these two cellular states are better known and key to understanding satellite cell dormancy. This will allow us to describe dormancy and its prerequisites.
脊椎动物的骨骼肌具有巨大的再生能力。在遭受不同类型的损伤后被破坏时，这个器官能够非常迅速地（在小鼠中注射肌毒素后不到20天）完全再生，并且可以反复再生。负责这种再生的细胞就是所谓的卫星细胞，即位于肌纤维之上的肌肉干细胞，肌纤维是一种巨大的多核细胞，含有收缩物质。当注射到肌肉中时，卫星细胞可以有效地分化为收缩性肌纤维。卫星细胞显示出巨大的治疗潜力；其再生能力在肌肉退化领域引发了特别的关注。在这篇综述中，我们将聚焦于卫星细胞的一个特殊特性：其静止和休眠状态。事实上，成年卫星细胞是静止的；它们位于肌纤维的基膜和基底膜之间，随时准备增殖并融合，以便在受伤时再生肌纤维。最近的研究表明，在人类和小鼠尸体中，卫星细胞的一个亚群能够进入休眠状态。与静止细胞相比，休眠的定义是代谢状态低、迁移性低以及在体外培养时分裂前有很长的延迟期。这个定义也是基于目前对长期造血干细胞的了解，造血干细胞的一个亚群基于相同的标准（与更频繁分裂的子代相比，分裂罕见且代谢低）被描述为处于休眠状态。在这篇综述的第一部分，我们将描述卫星细胞的静止状态。然后我们将聚焦于卫星细胞在肌肉中的不均匀分布，并描述证据表明它们的休眠状态在不同肌肉之间存在差异，因此在对这种细胞状态进行概括时应谨慎。在第二部分，我们将讨论发育动物中活跃分裂细胞向静止状态的转变。这种机制可能在从静止状态向休眠状态的转变中被利用或放大。在第三部分，我们将综述积极维持卫星细胞静止的信号和动态过程。对这些机制的深入理解是描述休眠如何依赖于细胞静止状态的关键。在第四部分，我们将探讨休眠本身：如何获得休眠的卫星细胞、它们的特征、代谢概况以及与静止细胞相比的分子特征。在这里，我们将强调最近最重要的发现之一：静止状态是卫星细胞进入休眠的先决条件。由于休眠是一个新发现的现象，我们将综述负责静止和激活的机制，因为这两种细胞状态更为人所知，也是理解卫星细胞休眠的关键。这将使我们能够描述休眠及其先决条件。
