Detailed characterization of the cell types in the human brain requires scalable experimental approaches to examine multiple aspects of the molecular state of individual cells, as well as computational integration of the data to produce unified cell-state annotations. Here we report improved high-throughput methods for single-nucleus droplet-based sequencing (snDrop-seq) and single-cell transposome hypersensitive site sequencing (scTHS-seq). We used each method to acquire nuclear transcriptomic and DNA accessibility maps for >60,000 single cells from human adult visual cortex, frontal cortex, and cerebellum. Integration of these data revealed regulatory elements and transcription factors that underlie cell-type distinctions, providing a basis for the study of complex processes in the brain, such as genetic programs that coordinate adult remyelination. We also mapped disease-associated risk variants to specific cellular populations, which provided insights into normal and pathogenic cellular processes in the human brain. This integrative multi-omics approach permits more detailed single-cell interrogation of complex organs and tissues.

中文翻译：

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人类成年大脑中转录和表观遗传状态的整合式单细胞分析。

人脑中细胞类型的详细表征需要可扩展的实验方法来检查单个细胞分子状态的多个方面，以及数据的计算集成以产生统一的细胞状态注释。在这里，我们报告了改进的高通量方法，用于基于单核液滴的测序（snDrop-seq）和单细胞转座体超敏位点测序（scTHS-seq）。我们使用每种方法从成人视觉皮层，额叶皮层和小脑中获取> 60,000个单细胞的核转录组和DNA可及性图。这些数据的整合揭示了构成细胞类型差异的调节元件和转录因子，为研究大脑中的复杂过程提供了基础，例如协调成人髓鞘再生的基因程序。我们还将与疾病相关的风险变体映射到特定的细胞群体，从而提供了对人脑中正常和致病性细胞过程的见解。这种集成的多组学方法可以对复杂的器官和组织进行更详细的单细胞询问。