Laboratory for Neuronal Circuit Dynamics, Imperial College London, London W12 0NN, UK.
Department of Psychiatry, Department of Clinical Research, University of Southern Denmark, 5230 Odense, Denmark.
Int J Mol Sci. 2022 Aug 16;23(16):9188. doi: 10.3390/ijms23169188.
DNA methylation profiling has become a promising approach towards identifying biomarkers of neuropsychiatric disorders including autism spectrum disorder (ASD). Epigenetic markers capture genetic risk factors and diverse exogenous and endogenous factors, including environmental risk factors and complex disease pathologies. We analysed the differential methylation profile of a regulatory region of the gene using cerebral organoids generated from induced pluripotent stem cells (iPSCs) from adults with a diagnosis of ASD and from age- and gender-matched healthy individuals. Both groups showed high levels of methylation across the majority of CpG sites within the profiled region of interest. The ASD group exhibited a higher number of unique DNA methylation patterns compared to controls and an increased CpG-wise variance. We detected six differentially methylated CpG sites in ASD, three of which reside within a methylation-dependent transcription factor binding site. In ASD, is subject to differential methylation patterns that may not only influence its expression, but may also indicate variable epigenetic regulation among cells.
DNA 甲基化分析已成为鉴定神经精神疾病生物标志物的一种很有前途的方法，包括自闭症谱系障碍（ASD）。表观遗传标记可以捕获遗传风险因素以及各种外源性和内源性因素，包括环境风险因素和复杂的疾病病理。我们使用从患有 ASD 的成年人和年龄及性别匹配的健康个体诱导多能干细胞（iPSC）生成的大脑类器官分析了 基因的调控区域的差异甲基化谱。两组在分析的感兴趣区域的大多数 CpG 位点上均表现出高度甲基化。与对照组相比，ASD 组表现出更多独特的 DNA 甲基化模式，CpG -wise 方差也增加。我们在 ASD 中检测到六个差异甲基化的 CpG 位点，其中三个位于依赖甲基化的转录因子结合位点内。在 ASD 中， 受到差异甲基化模式的影响，这不仅可能影响其表达，还可能表明细胞之间存在可变的表观遗传调控。
