Metabolomic insights into system-wide coordination of vertebrate metamorphosis.
Metabolomic insights into system-wide coordination of vertebrate metamorphosis.
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DOI：
10.1186/1471-213x-14-5
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发表时间：
2014-02-05
影响因子：
--
通讯作者：
Helbing CC
中科院分区：
文献类型：
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作者：
Ichu TA;Han J;Borchers CH;Lesperance M;Helbing CC
在胚胎发生完成后，许多生物体经历额外的强制性发育过渡，以获得实质上不同的幼年或成年形式。在无尾类动物的变态过程中，水生蝌蚪经历了剧烈的形态变化和组织器官的重塑，成为一只幼蛙。甲状腺激素是启动这一过程所必需的，但器官和组织之间协调许多必要变化的机制却知之甚少。代谢产物通常是物种之间高度保守的生物分子，并且是表型的最接近的反映。由于血液在整个生物体中的广泛分布，对其中所含代谢物的检查提供了变态期间所经历的协调变化的全系统概述。我们进行了非靶向代谢组学分析的血清样品从自然变态的牛蛙蝌蚪蛙蛙使用超高效液相色谱仪耦合到质谱仪。从每份血清样本中获得总代谢物和水性代谢物提取物，以分别选择非极性和极性代谢物，并通过运行真实化合物对所选代谢物进行验证。大多数检测到的代谢物（74%）在变质阶段之间表现出统计学上显著的丰度变化（padj < 0.001）。我们观察到五个核心代谢途径的广泛重塑：精氨酸和嘌呤/嘧啶，半胱氨酸/甲硫氨酸，鞘脂，类花生酸代谢和尿素循环，并发现在这个胚后过程中的脂质的主要作用的证据。传统上与人类疾病状态相关的代谢物被发现与导致明显形态学变化的事件期间发生的系统范围的变化具有生物学联系。据我们所知，这是第一个大规模的代谢组学研究脊椎动物变态确定基本途径参与协调这一重要的发展过程，并铺平了道路代谢组学研究其他变质系统，包括鱼类和昆虫。
After completion of embryogenesis, many organisms experience an additional obligatory developmental transition to attain a substantially different juvenile or adult form. During anuran metamorphosis, the aquatic tadpole undergoes drastic morphological changes and remodelling of tissues and organs to become a froglet. Thyroid hormones are required to initiate the process, but the mechanism whereby the many requisite changes are coordinated between organs and tissues is poorly understood. Metabolites are often highly conserved biomolecules between species and are the closest reflection of phenotype. Due to the extensive distribution of blood throughout the organism, examination of the metabolites contained therein provides a system-wide overview of the coordinated changes experienced during metamorphosis. We performed an untargeted metabolomic analysis on serum samples from naturally-metamorphosing Rana catesbeiana from tadpoles to froglets using ultraperformance liquid chromatography coupled to a mass spectrometer. Total and aqueous metabolite extracts were obtained from each serum sample to select for nonpolar and polar metabolites, respectively, and selected metabolites were validated by running authentic compounds. The majority of the detected metabolites (74%) showed statistically significant abundance changes (padj < 0.001) between metamorphic stages. We observed extensive remodelling of five core metabolic pathways: arginine and purine/pyrimidine, cysteine/methionine, sphingolipid, and eicosanoid metabolism and the urea cycle, and found evidence for a major role for lipids during this postembryonic process. Metabolites traditionally linked to human disease states were found to have biological linkages to the system-wide changes occuring during the events leading up to overt morphological change. To our knowledge, this is the first wide-scale metabolomic study of vertebrate metamorphosis identifying fundamental pathways involved in the coordination of this important developmental process and paves the way for metabolomic studies on other metamorphic systems including fish and insects.