Metabolic biomarkers of prenatal alcohol exposure in human embryonic stem cell-derived neural lineages.
Metabolic biomarkers of prenatal alcohol exposure in human embryonic stem cell-derived neural lineages.
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DOI：
10.1111/j.1530-0277.2011.01732.x
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Cezar GG
中科院分区：
文献类型：
--
作者：
Palmer JA;Poenitzsch AM;Smith SM;Conard KR;West PR;Cezar GG
胎儿酒精谱系障碍（FASD）是神经发育障碍的主要原因。FASD的潜在机制尚未完全了解，并且缺乏识别风险的生物标志物。在这里，我们进行代谢组学分析的胚状体和神经谱系来源于人胚胎干细胞（hES），以确定神经分泌组响应乙醇暴露。WA 01和WA 09 hES细胞分化为胚状体、神经祖细胞或神经元。将细胞沿着这一进程用0%、0.1%或0.3%乙醇培养4天。对上清液进行C18色谱，然后进行ESI-QTOF-MS。使用公共数据库注释特征，并用纯化标准品和比较MS/MS确认四种推定生物标志物的身份。乙醇处理诱导人胚状体（180个特征）、神经祖细胞（76个特征）和神经元（42个特征）中代谢物丰度的统计学显著变化。不同细胞类型之间没有共同的显著特征。15个特征显示了对乙醇的剂量反应。确认了四种化学身份：L-甲状腺素、5 '-甲硫腺苷和色氨酸代谢物L-犬尿氨酸和吲哚乙醛。一个功能与琥珀酰腺苷的推定注释显着增加，在两种乙醇治疗。其他特征对乙醇处理具有选择性，但在公共数据库中没有注释。乙醇暴露诱导人胚状体、神经祖细胞和神经元的代谢组谱发生统计学显著变化。这些代谢物中的几种通常存在于人血清中，表明它们作为潜在的血清FASD生物标志物的有用性。这些研究结果表明，在发育中的神经系统和酒精损伤的机制描绘乙醇的影响的生化途径在人类发展。
Fetal alcohol spectrum disorders (FASD) are a leading cause of neurodevelopmental disability. The mechanisms underlying FASD are incompletely understood, and biomarkers to identify those at risk are lacking. Here, we perform metabolomic analysis of embryoid bodies and neural lineages derived from human embryonic stem (hES) cell to identify the neural secretome produced in response to ethanol exposure. WA01 and WA09 hES cells were differentiated into embryoid bodies, neural progenitors or neurons. Cells along this progression were cultured for four days with 0%, 0.1% or 0.3% ethanol. Supernatants were subjected to C18 chromatography followed by ESI-QTOF-MS. Features were annotated using public databases and the identities of four putative biomarkers were confirmed with purified standards and comparative MS/MS. Ethanol treatment induced statistically significant changes to metabolite abundance in human embryoid bodies (180 features), neural progenitors (76 features) and neurons (42 features). There were no shared significant features between different cell types. Fifteen features showed a dose-response to ethanol. Four chemical identities were confirmed; L-thyroxine, 5’-methylthioadenosine, and the tryptophan metabolites L-kynurenine, and indoleacetaldehyde. One feature with a putative annotation of succinyladenosine was significantly increased in both ethanol treatments. Additional features were selective to ethanol treatment but were not annotated in public databases. Ethanol exposure induces statistically significant changes to the metabolome profile of human embryoid bodies, neural progenitors and neurons. Several of these metabolites are normally present in human serum, suggesting their usefulness as potential serum FASD biomarkers. These findings suggest the biochemical pathways that are affected by ethanol in the developing nervous system and delineate mechanisms of alcohol injury during human development.
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影响因子：
4
作者：
Cezar, Gabriela G.;Quam, Jessica A.;Muotri, Alysson R.
通讯作者：
Muotri, Alysson R.
DOI：
10.1002/bdrb.20182
发表时间：
2009-02-01
影响因子：
--
作者：
Chirino-Galindo, Gladys;Baiza-Gutman, Luis A.;Palomar-Morales, Martin
通讯作者：
Palomar-Morales, Martin
DOI：
10.1111/j.1530-0277.1990.tb00503.x
发表时间：
1990-06-01
期刊：
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
影响因子：
--
作者：
HANNIGAN, JH;BELLISARIO, RL
通讯作者：
BELLISARIO, RL
DOI：
10.1016/s0378-4347(99)00024-9
发表时间：
1999-04-16
期刊：
JOURNAL OF CHROMATOGRAPHY B
影响因子：
--
作者：
Krijt, J;Kmoch, S;Sebesta, I
通讯作者：
Sebesta, I
影响因子：
4
作者：
Latchney, Sarah E.;Lioy, Daniel T.;Opanashuk, Lisa A.
通讯作者：
Opanashuk, Lisa A.