Identification of small molecules from human embryonic stem cells using metabolomics
Identification of small molecules from human embryonic stem cells using metabolomics
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DOI：
10.1089/scd.2007.0022
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发表时间：
2007-12-01
影响因子：
4
通讯作者：
Muotri, Alysson R.
中科院分区：
文献类型：
--
作者：
Cezar, Gabriela G.;Quam, Jessica A.;Muotri, Alysson R.
代谢组学使得能够发现可用作药理学功效或毒性的候选生物标志物的小分子。人类发育的生化途径可能在人类胚胎干细胞（hES）及其衍生物中活跃，因为它们在体外重演器官发生。我们假设，小分子可以从未分化的hES细胞和hES细胞衍生的神经前体（hNP）使用代谢组学测量，这些化合物在响应人类发育的已知干扰物时发生改变。在暴露于丙戊酸盐（一种神经发育障碍诱导剂）后，在hES细胞和hNP中进行代谢产物分析。犬尿氨酸（色氨酸代谢的中间体）和谷氨酸代谢中的其他小分子在丙戊酸盐反应中显著上调。因此，我们第一次能够测量和鉴定从hES细胞和衍生自hES细胞的细胞分泌的小分子。因此，hES细胞代谢组可以作为候选生物标志物的来源，以预测或测量药理学功效或毒性反应。
Metabolomics enables the discovery of small molecules that may serve as candidate biomarkers of pharmacological efficacy or toxicity. Biochemical pathways of human development are likely active in human embryonic stem (hES) cells and derivatives, since they recapitulate organogenesis in vitro. We hypothesized that small molecules could be measured from undifferentiated hES cells and hES cell-derived neural precursors (hNPs) using metabolomics and that these compounds are altered in response to known disruptors of human development. Metabolite profiling was performed in hES cells and hNPs after exposure to valproate, an inducer of neurodevelopmental disorders. Kynurenine, an intermediate in tryptophan metabolism, and other small molecules in glutamate metabolism were significantly upregulated in response to valproate. Thus, for the first time, we have been able to measure and identify small molecules secreted from hES cells and cells derived from hES cells. The hES cell metabolome may thus serve as a source of candidate biomarkers to predict or measure pharmacological efficacy or toxic response.