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Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain (snDrop-seq)
Lake, Blue B and Chen, Song and Sos, Brandon C and Fan, Jean and Kaeser, Gwendolyn E and Yung, Yun C and Duong, Thu E and Gao, Derek and Chun, Jerold and Kharchenko, Peter V and others
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.