Individual Variability in Human Cell Type Transcriptomes and Epigenomes [YF2A]

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 30 years old female.

多样性与个体差异是人类认知功能的核心基础。鉴定大脑细胞组分中保守与可变的（表）基因组特征，是解析大脑功能个体差异的神经生物学机制的关键环节。我们针对11名年龄跨度23至74岁的成年人类供体的前额叶皮层布罗德曼分区BA46（Broadmann Area BA46）神经元，采用单细胞核甲基化组与转录组测序（single nucleus methylome and transcriptome sequence, snmCT-seq）技术进行检测。我们基于甲基化特征将细胞聚类为不同的脑细胞类型，随后在不同供体与同一供体内部，对各细胞类型的转录组与表观基因组特征进行分析。依托单细胞多组学检测数据，我们同时解析了RNA表达水平与甲基化水平之间的关联。本数据集纳入了性别与年龄均具多样性的供体样本，通过多组学检测手段，旨在探究大脑功能个体间差异的相关维度。
实验设计：我们采用snmCT-seq技术，对成年人类前额叶皮层神经元的转录组与表观基因组特征进行鉴定，供体群体包括3名老年男性（年龄区间70~71岁）、3名老年女性（71~74岁）、3名青年男性（25岁）以及2名青年女性（23~30岁）。针对每名供体，我们采集两份脑组织切块并分别进行处理，以评估供体内的细胞异质性。本次样本来自一名30岁女性供体的A组分脑组织。