A Cell Epigenotype Specific Model for the Correction of Cellular Heterogeneity in the Brain. Homo sapiens

Cellular heterogeneity may bias cell type specific epigenetic patterns leading to a dramatic increase in false positive or negative findings in psychiatric epigenetic studies. To address this issue, we performed fluorescence activated cell sorting (FACS) of neuronal nuclei in post mortem frontal cortex 58 samples followed by Illumina HM450 microarray based DNA methylation profiling. We characterized the extent of neuron and glia specific DNA methylation variation independent of disease status and identified significant cell type specific epigenetic variation at 51% of loci. Overall design: DNA methylation was profiled for sorted neuronal nuclei from post mortem frontal cortex of 29 major depression and 29 matched control samples using Illumina HM450 microarrays

细胞异质性可能会干扰细胞类型特异性表观遗传模式，进而导致精神疾病表观遗传研究中假阳性或假阴性结果大幅增加。为解决这一问题，我们对58例死后额叶皮层样本的神经元细胞核开展了荧光激活细胞分选（Fluorescence Activated Cell Sorting，FACS），随后基于Illumina HM450微阵列进行DNA甲基化谱分析。我们表征了不受疾病状态影响的神经元与胶质细胞特异性DNA甲基化变异程度，并在51%的基因位点上发现了显著的细胞类型特异性表观遗传变异。实验整体设计：采用Illumina HM450微阵列，对29例重度抑郁症患者及29例匹配对照个体的死后额叶皮层分选神经元细胞核进行DNA甲基化谱分析。