Extraocular muscle satellite cells are high performance myo-engines retaining efficient regenerative capacity in dystrophin deficiency.

Extraocular muscle satellite cells are high performance myo-engines retaining efficient regenerative capacity in dystrophin deficiency.
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DOI:
10.1016/j.ydbio.2014.08.035
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发表时间:
2015-01-01
影响因子:
2.7
通讯作者:
Yablonka-Reuveni, Zipora
Yablonka-Reuveni, Zipora
中科院分区:
生物学3区
文献类型:
--
作者:
Stuelsatz, Pascal;Shearer, Andrew;Li, Yunfei;Muir, Lindsey A.;Ieronimakis, Nicholas;Shen, Qingwu W.;Kirillova, Irina;Yablonka-Reuveni, Zipora

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眼外肌是一种高度特化的骨骼肌,起源于头部中胚层,控制眼球运动。眼外肌在杜氏肌营养不良症和肌营养不良蛋白缺乏症的动物模型中是唯一幸免的。肌源性祖细胞的特定性状可能是这种优先保留的决定因素,但对该肌群中的肌源性细胞知之甚少。虽然卫星细胞(SC)长期以来被认为是成人肌肉中肌源性细胞的主要来源,但有关这些细胞的大多数知识来自原型肢体肌肉。在这项研究中,我们发现,EOM,无论其独特的Pax 3阴性谱系起源,都与其肢体和膈肌体节衍生的对应物共享共同的签名(Pax 7+,Ki 67 −,Nestin-GFP+,Myf 5 nLacZ+,MyoD阳性谱系起源),但在细胞培养试验中显示,它们具有显着的高增殖潜力。具体而言,我们证明,在成年以及在老龄小鼠,眼外肌干细胞具有上级的扩展能力,贡献显着更多的增殖,分化和更新后代比他们的肢体和隔膜的同行。这些稳健的生长和更新特性由分离自肌营养不良蛋白缺失(mdx)小鼠的EOM SC维持,而来自受肌营养不良蛋白缺乏影响的肌肉的SC(即,肢体和隔膜)在体外扩张不良。在将供体细胞移植到宿主mdx肢体肌肉中的细胞移植测定中,EOM SC也保持了更高的性能。总的来说,我们的研究提供了眼外肌肌源性祖细胞的全面情况,表明虽然这些细胞与体节衍生肌肉中的原型SC具有共同的特征,但它们具有强大的生长和更新能力,这保证了高性能肌发动机的称号,并促进考虑它们的特性,以开发基于细胞的治疗新方法来对抗骨骼肌萎缩。
Extraocular muscles (EOMs) are highly specialized skeletal muscles that originate from the head mesoderm and control eye movements. EOMs are uniquely spared in Duchenne muscular dystrophy and animal models of dystrophin deficiency. Specific traits of myogenic progenitors may be determinants of this preferential sparing, but very little is known about the myogenic cells in this muscle group. While satellite cells (SCs) have long been recognized as the main source of myogenic cells in adult muscle, most of the knowledge about these cells comes from the prototypic limb muscles. In this study, we show that EOMs, regardless of their distinctive Pax3-negative lineage origin, harbor SCs that share a common signature (Pax7+, Ki67−, Nestin-GFP+, Myf5nLacZ+, MyoD-positive lineage origin) with their limb and diaphragm somite-derived counterparts, but are remarkably endowed with a high proliferative potential as revealed in cell culture assays. Specifically, we demonstrate that in adult as well as in aging mice, EOM SCs possess a superior expansion capacity, contributing significantly more proliferating, differentiating and renewal progeny than their limb and diaphragm counterparts. These robust growth and renewal properties are maintained by EOM SCs isolated from dystrophin-null (mdx) mice, while SCs from muscles affected by dystrophin deficiency (i.e., limb and diaphragm) expand poorly in vitro. EOM SCs also retain higher performance in cell transplantation assays in which donor cells were engrafted into host mdx limb muscle. Collectively, our study provides a comprehensive picture of EOM myogenic progenitors, showing that while these cells share common hallmarks with the prototypic SCs in somite-derived muscles, they distinctively feature robust growth and renewal capacities that warrant the title of high performance myo-engines and promote consideration of their properties for developing new approaches in cell-based therapy to combat skeletal muscle wasting.
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发表时间: 2012-09
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