Heterogeneous activation of a slow myosin gene in proliferating myoblasts and differentiated single myofibers.
Heterogeneous activation of a slow myosin gene in proliferating myoblasts and differentiated single myofibers.
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DOI：
10.1016/j.ydbio.2015.02.025
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发表时间：
2015-06-01
影响因子：
2.7
通讯作者：
Kuang, Shihuan
中科院分区：
文献类型：
--
作者：
Wang, Jing-hua;Wang, Qiao-jing;Wang, Chao;Reinholt, Brad;Grant, Alan L.;Gerrard, David E.;Kuang, Shihuan
每个骨骼肌都包含固定比例的快肌纤维和慢肌纤维，它们以刻板的模式分布，以实现特定的运动功能。肌纤维在发育和再生过程中是如何被指定的还知之甚少。在这里，我们解决这个问题，使用转基因报告小鼠，不可磨灭的标记的肌纤维谱系的基础上激活快或慢肌球蛋白。谱系追踪表明，在发育过程中，所有的肌肉都激活了快肌球蛋白基因Myl1，但不是慢肌球蛋白基因Myh7，它在所有慢肌纤维中被激活，但在快肌纤维的一个子集中被激活。类似地，大多数新生肌纤维在快速肌肉再生期间不激活Myh7，但在再生完成时恢复了快肌纤维和慢肌纤维的比例和模式。在单个肌纤维水平上，大多数成熟的快肌纤维的核组成是不均匀的，表现为Myh 7的镶嵌激活。引人注目的是，Myh7在共表达成肌祖细胞标志物Pax7的增殖成肌细胞亚群中被激活。当被诱导分化时，Myh7活化的成肌细胞比未活化的成肌细胞更容易分化，并且具有更高的倾向，但不限于成为慢肌管。总之，我们的数据揭示了一个单一的肌纤维内显着的核异质性，并挑战传统的观点，肌球蛋白基因只表达肌分化后。这些结果提供了新的见解肌纤维类型规格的调节。
Each skeletal muscle contains a fixed ratio of fast and slow myofibers that are distributed in a stereotyped pattern to achieve a specific motor function. How myofibers are specified during development and regeneration is poorly understood. Here we address this question using transgenic reporter mice that indelibly mark the myofiber lineages based on activation of fast or slow myosin. Lineage tracing indicates that during development all muscles have activated the fast myosin gene Myl1, but not the slow myosin gene Myh7, which is activated in all slow but a subset of fast myofibers. Similarly, most nascent myofibers do not activate Myh7 during fast muscle regeneration, but the ratio and pattern of fast and slow myofibers are restored at the completion of regeneration. At the single myofiber level, most mature fast myofibers are heterogeneous in nuclear composition, manifested by mosaic activation of Myh7. Strikingly, Myh7 is activated in a subpopulation of proliferating myoblasts that co-express the myogenic progenitor marker Pax7. When induced to differentiate, the Myh7-activated myoblasts differentiate more readily than the non-activated myoblasts, and have a higher tendency, but not restricted, to become slow myotubes. Together, our data reveal significant nuclear heterogeneity within a single myofiber, and challenge the conventional view that myosin genes are only expressed after myogenic differentiation. These results provide novel insights into the regulation of muscle fiber type specification.
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影响因子：
4.8
作者：
Parsons, SA;Millay, DP;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
9.8
作者：
Wang YX;Zhang CL;Yu RT;Cho HK;Nelson MC;Bayuga-Ocampo CR;Ham J;Kang H;Evans RM
通讯作者：
Evans RM
影响因子：
15.9
作者：
Colbert, MC;Hall, DG;Robbins, J
通讯作者：
Robbins, J
DOI：
10.1083/jcb.200312007
发表时间：
2004-08-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Zammit PS;Golding JP;Nagata Y;Hudon V;Partridge TA;Beauchamp JR
通讯作者：
Beauchamp JR
影响因子：
2.7
作者：
Olguin, HC;Olwin, BB
通讯作者：
Olwin, BB