Integrative Single-Cell Analysis By Transcriptional And Epigenetic States In Human Adult Brain

Abstract

Detailed characterization of the cell types comprising the highly complex human brain is essential to understanding its function. Such tasks require highly scalable experimental approaches to examine different aspects of the molecular state of individual cells, as well as the computational integration to produce unified cell state annotations. Here we report the development of two highly scalable methods (snDrop-Seq and scTHS-Seq), that we have used to acquire nuclear transcriptome and DNA accessibility maps for thousands of single cells from the human adult visual and frontal cortex. This has led to the best-resolved human neuronal subtypes to date, identification of a majority of the non-neuronal cell types, as well as the cell-type specific nuclear transcriptome and DNA accessibility maps. Integrative analysis allowed us to identify transcription factors and regulatory elements shaping the state of different brain cell types, and to map genetic risk factors of human brain common diseases to specific pathogenic cell types and subtypes.