Glycogenome expression dynamics during mouse C2C12 myoblast differentiation suggests a sequential reorganization of membrane glycoconjugates
Glycogenome expression dynamics during mouse C2C12 myoblast differentiation suggests a sequential reorganization of membrane glycoconjugates
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DOI：
10.1186/1471-2164-10-483
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发表时间：
2009-10-20
期刊：
影响因子：
4.4
通讯作者：
Dupuy, Fabrice
中科院分区：
文献类型：
--
作者：
Janot, Mathilde;Audfray, Aymeric;Dupuy, Fabrice
背景：为了获得对骨骼肌发生的新的分子认识，已经应用了几种全球转录组和蛋白质组学方法，但没有一种方法产生关于糖基因组表达的任何特定数据，从而关于糖结构在这一过程中的作用，尽管糖共轭参与了包括分化和发育在内的各种生物学事件。结果：在276个基因中，95个基因在C2C12细胞分化为肌管时表达发生改变，37个基因表达上调或下调4倍以上。表达动态的主成分分析和层次成分分析确定了三组协同和顺序调控的基因。第一组包括12个表达下调的基因，第二组有4个基因在分化后24小时达到表达高峰，最后21个基因表达上调。这些基因主要编码细胞黏附分子和参与糖胺多聚糖和糖脂生物合成的关键酶(新乳糖系列、乳糖系列和神经节系列)，为细胞融合前质膜和细胞外基质的修饰提供了更清晰的指示。特别是，成肌细胞表面神经节苷脂GM3的数量增加提示其在成肌分化的初始阶段具有潜在的作用。结论：这些结果首次为C2C12分化过程中糖基因的表达动态提供了广泛的描述。在37个高度失控的糖基因中，29个从未与肌肉发生相关。它们的生物学功能暗示了葡聚糖在骨骼肌发生中的新作用。
Background: Several global transcriptomic and proteomic approaches have been applied in order to obtain new molecular insights on skeletal myogenesis, but none has generated any specific data on glycogenome expression, and thus on the role of glycan structures in this process, despite the involvement of glycoconjugates in various biological events including differentiation and development. In the present study, a quantitative real-time RT-PCR technology was used to profile the dynamic expression of 375 glycogenes during the differentiation of C2C12 myoblasts into myotubes.Results: Of the 276 genes expressed, 95 exhibited altered mRNA expression when C2C12 cells differentiated and 37 displayed more than 4-fold up-or down-regulations. Principal Component Analysis and Hierarchical Component Analysis of the expression dynamics identified three groups of coordinately and sequentially regulated genes. The first group included 12 down-regulated genes, the second group four genes with an expression peak at 24 h of differentiation, and the last 21 up-regulated genes. These genes mainly encode cell adhesion molecules and key enzymes involved in the biosynthesis of glycosaminoglycans and glycolipids (neolactoseries, lactoseries and ganglioseries), providing a clearer indication of how the plasma membrane and extracellular matrix may be modified prior to cell fusion. In particular, an increase in the quantity of ganglioside GM3 at the cell surface of myoblasts is suggestive of its potential role during the initial steps of myogenic differentiation.Conclusion: For the first time, these results provide a broad description of the expression dynamics of glycogenes during C2C12 differentiation. Among the 37 highly deregulated glycogenes, 29 had never been associated with myogenesis. Their biological functions suggest new roles for glycans in skeletal myogenesis.