Stem Cells as a Good Tool to Investigate Dysregulated Biological Systems in Autism Spectrum Disorders
Stem Cells as a Good Tool to Investigate Dysregulated Biological Systems in Autism Spectrum Disorders
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DOI：
10.1002/aur.1296
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发表时间：
2013-10-01
期刊：
影响因子：
4.7
通讯作者：
Passos-Bueno, Maria Rita
中科院分区：
文献类型：
--
作者：
Griesi-Oliveira, Karina;Sunaga, Daniele Yumi;Passos-Bueno, Maria Rita
自闭症谱系障碍(ASD)的遗传异质性阻碍了对其病因的认识；然而，导致ASD的不同基因改变似乎与常见的分子通路或生物学过程的干扰有关。在这种情况下，寻找ASD患者和对照组之间的差异表达基因(DEG)是确定此类疾病的分子病因学的一个很好的替代方案。在这里，我们使用全基因组表达分析来比较特发性自闭症患者(n=7)和对照样本(n=6)人类脱落乳牙(SHED)干细胞的转录组。在已鉴定的683个DEG中，近一半在大脑中表达(P=0.003)，其中相当多的DEG参与了先前与自闭症相关的机制，如蛋白质合成、细胞骨架调节、细胞黏附和选择性剪接，这些机制证实了使用SHEDS来解开自闭症的原因。自闭症患者还表现出受雄激素受体(AR)及其自身调节的基因过度表达，而AR本身又与CHD8(染色域解旋酶DNA结合蛋白8)相互作用，CHD8基因最近被证明与自闭症的原因有关，在这里测试的一些患者中发现表达上调。这些数据为CHD8导致这些疾病的机制提供了理论基础。综上所述，我们的结果表明ASD参与了非调控的通路，并揭示了SHEDS代表了一种可供选择的细胞来源，可用于理解ASD的发病机制。自闭症研究报告2013，..：..-.(C)2013年国际自闭症研究学会，Wiley期刊公司。
Identification of the causes of autism spectrum disorders (ASDs) is hampered by their genetic heterogeneity; however, the different genetic alterations leading to ASD seem to be implicated in the disturbance of common molecular pathways or biological processes. In this scenario, the search for differentially expressed genes (DEGs) between ASD patients and controls is a good alternative to identify the molecular etiology of such disorders. Here, we employed genome-wide expression analysis to compare the transcriptome of stem cells of human exfoliated deciduous teeth (SHEDs) of idiopathic autistic patients (n=7) and control samples (n=6). Nearly half of the 683 identified DEGs are expressed in the brain (P=0.003), and a significant number of them are involved in mechanisms previously associated with ASD such as protein synthesis, cytoskeleton regulation, cellular adhesion and alternative splicing, which validate the use of SHEDs to disentangle the causes of autism. Autistic patients also presented overexpression of genes regulated by androgen receptor (AR), and AR itself, which in turn interacts with CHD8 (chromodomain helicase DNA binding protein 8), a gene recently shown to be associated with the cause of autism and found to be upregulated in some patients tested here. These data provide a rationale for the mechanisms through which CHD8 leads to these diseases. In summary, our results suggest that ASD share deregulated pathways and revealed that SHEDs represent an alternative cell source to be used in the understanding of the biological mechanisms involved in the etiology of ASD. Autism Res 2013, ..: ..-... (c) 2013 International Society for Autism Research, Wiley Periodicals, Inc.