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. 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.

多样性与个体差异是人类认知功能的核心基础。精准鉴定大脑细胞组分中保守与可变的（表观）基因组特征，对于解析大脑功能个体差异的神经生物学基础具有关键意义。我们针对11名年龄跨度23至74岁、涵盖两性的成年人类捐献者的前额叶皮层（布罗德曼分区Brodmann Area, BA46）神经元，应用了单细胞核甲基化-转录组测序（single nucleus methylome and transcriptome sequence, snmCT-seq）技术。我们基于甲基化特征将细胞聚类为不同脑细胞类型，随后针对每一类细胞，分析了不同捐献者间以及同一捐献者内部的转录组与表观基因组特征差异。借助单细胞多模态检测数据，我们还解析了RNA表达与甲基化水平之间的关联。本数据集包含了来自性别与年龄均具有多样性的捐献者的多组学检测数据，旨在深入探究个体间差异的相关维度。我们进一步采用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，所纳入的捐献者包括3名老年男性（年龄区间70~71岁）、3名老年女性（71~74岁）、3名年轻男性（25岁）以及2名年轻女性（23~30岁）。针对每一名捐献者，我们均采集两份脑组织样本并分别进行处理，以评估同一捐献者内部的变异情况。本次所用样本来自一名73岁女性捐献者的脑组织A份。