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乙醇会改变正常和染色体异常的人类胚胎干细胞衍生神经球的增殖与分化。

Ethanol alters proliferation and differentiation of normal and chromosomally abnormal human embryonic stem cell-derived neurospheres.

作者信息

Krishnamoorthy Malini, Gerwe Brian A, Scharer Christopher D, Sahasranaman Vanita, Eilertson Carmen D, Nash Rachel J, Usta Sümeyra Naz, Kelly Shasmine, Rose Matthew, Peraza Rene, Arumugham Jagan, Stewart Bethany, Stice Steven L, Nash Rodney J

机构信息

Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, USA.

出版信息

Birth Defects Res B Dev Reprod Toxicol. 2013 Jun;98(3):283-95. doi: 10.1002/bdrb.21063. Epub 2013 May 21.

Abstract

Ethanol is a powerful substance and, when consumed during pregnancy, has significant psychoactive and developmental effects on the developing fetus. These abnormalities include growth retardation, neurological deficits, and behavioral and cognitive deficiencies, commonly referred to as fetal alcohol spectrum disorder. The effect of ethanol has been reported to affect cellular development on the embryonic level, however, not much is known about mutations contributing to the influence of ethanol. The purpose of our study was to determine if mutation contribute to changes in differentiation patterning, cell-cycle regulatory gene expression, and DNA methylation in human embryonic stem cells after ethanol exposure. We exposed human embryonic stem cells (with and without know DNA mutations) to a low concentration (20 mM) of ethanol and measured neurosphere proliferation and differentiation, glial protein levels, expression of various cell-cycle genes, and DNA methylation. Ethanol altered cell-cycle gene expression between the two cell lines; however, gene methylation was not affected in ether lines.

摘要

乙醇是一种强效物质,在孕期摄入时,会对发育中的胎儿产生显著的精神活性和发育影响。这些异常包括生长发育迟缓、神经缺陷以及行为和认知缺陷,通常被称为胎儿酒精谱系障碍。据报道,乙醇的影响在胚胎水平上会影响细胞发育,然而,对于导致乙醇影响的突变了解甚少。我们研究的目的是确定突变是否会导致乙醇暴露后人胚胎干细胞分化模式、细胞周期调控基因表达和DNA甲基化的变化。我们将人胚胎干细胞(已知有和没有DNA突变)暴露于低浓度(20 mM)乙醇中,并测量神经球增殖与分化、胶质蛋白水平、各种细胞周期基因的表达以及DNA甲基化情况。乙醇改变了两种细胞系之间的细胞周期基因表达;然而,两种细胞系中的基因甲基化均未受影响。

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