Journal Article

Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain

Yung, Yun C, Gao, Derek, Lake, Blue B, Duong, Thu E, Chun, Jerold, Zhang, Kun, Sos, Brandon C, Kaeser, Gwendolyn E, Chen, Song, Fan, Jean, Kharchenko, Peter V

2018

Overview

Single-cell analysis of the adult human brain is facilitated by improved methods for RNA-seq and hypersensitive-site mapping. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 38/39 / 38/91 / 45/23 / 45/62 / 45/91 / 631/1647/514/2254 / 631/208/177 / 631/208/514/1949 / 631/378/340 / Adult / Agriculture / Analysis / Annotations / Bioinformatics / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / Biomedicine / Biotechnology / Brain / Brain - metabolism / Brain mapping / Cerebellum / Cerebellum - metabolism / Cerebellum - pathology / Computational neuroscience / Cortex (frontal) / Deoxyribonucleic acid / DNA / DNA binding proteins / DNA sequencing / Epigenesis, Genetic - genetics / Epigenetic inheritance / Frontal Lobe - metabolism / Frontal Lobe - pathology / Gene mapping / Genetic aspects / Genetic programs / Health aspects / High-Throughput Nucleotide Sequencing / Humans / Integration / Interrogation / Life Sciences / Myelination / Nuclei (cytology) / Organs / Regulatory sequences / Sequence Analysis, RNA / Single-Cell Analysis - methods / Transcription (Genetics) / Transcription factors / Transcriptome - genetics / Visual cortex / Visual Cortex - metabolism / Visual Cortex - pathology