Individual Variability in Human Cell Type Transcriptomes and Epigenomes [OF2B]. Individual Variability in Human Cell Type Transcriptomes and Epigenomes [OF2B]

Diversity and individual variability are essential to human cognitive function. Identifying the conserved and variable (epi)genomic signatures of the brain’s cellular components is critical for understanding the neurobiological basis of individual variation in brain function. We applied single nucleus methylome and transcriptome sequence (snmCT-seq) to neurons from the frontal cortex of 11 adult human donors spanning a range of ages from 23 to 74, including males and females (Broadmann Area BA46). We clustered cells into brain cell types based on methylation features. We then examined the transcriptome and epigenome features in each cell type between and within individual donors. Taking advantage of the multimodal measurements in single cells, we also identified the relation between RNA expression and methylation level.These data with multiomics measurement from donors with sex and age diversity aims to approach the dimension of inter-individual variability. Overall design: We apply snmCT-seq to identify the transcriptomic and epigenomic features of neurons from individual adult human frontal cortex, including 3 aged male donors (age range 70-71), 3 aged female donors (71-74 years old), 3 young male donors (25 years old) and 2 young female donors (23-30 years old). For each donor, 2 chunks of brain tissue were collected and processed separately, to assess within-donor variability. This sample is from chunk A of a 73 years old female.

多样性与个体变异性是人类认知功能的核心基础。解析大脑细胞组分中保守且可变的（表观）基因组特征，对于阐明脑功能个体差异的神经生物学基础至关重要。我们针对11名成年人类供体的前额叶皮层神经元，应用单细胞核甲基化组与转录组测序（single nucleus methylome and transcriptome sequence，简称snmCT-seq）；该批供体年龄跨度为23至74岁，涵盖男性与女性，样本取自布罗德曼分区（Broadmann Area）BA46。我们基于甲基化特征将细胞聚类为不同脑细胞类型，随后分析了各细胞类型在不同供体间以及同一供体内的转录组与表观基因组特征。借助单细胞的多模态测量数据，我们还鉴定了RNA表达水平与甲基化水平之间的关联。本数据集包含来自性别与年龄均具多样性的供体的多组学测量数据，旨在探究个体间变异性的相关维度。
整体实验设计：我们通过snmCT-seq鉴定成年人类前额叶皮层神经元的转录组与表观基因组特征，共纳入3名老年男性供体（年龄区间70-71岁）、3名老年女性供体（71-74岁）、3名青年男性供体（25岁）以及2名青年女性供体（23-30岁）。我们为每名供体采集两份脑组织块并分别进行处理，以评估供体内的变异情况。本次样本取自1名73岁女性供体的A组脑组织块。