An ultra high-throughput method for single-cell joint analysis of open chromatin and transcriptome

Simultaneous profiling of transcriptome and chromatin accessibility within single cells is a powerful approach to dissect gene regulatory programs in complex tissues. However, the current tools are limited by modest throughput. We now describe an ultra high-throughput method, Paired-seq, for parallel analysis of transcriptome and accessible chromatin in millions of single cells. We demonstrate the utility of Paired-seq for analyzing the dynamic and cell-type specific gene regulatory programs in complex tissues, by applying it to mouse adult cerebral cortex and fetal forebrain. The joint profiles of a large number of single cells allowed us to deconvolute the transcriptome and open chromatin landscapes in the major cell types within these brain tissues, infer putative target genes of candidate enhancers, and reconstruct the trajectory of cellular lineages within the developing forebrain. *** Processed files of brain cells can be downloaded from: https://github.com/cxzhu/Paired-seq/tree/master/matrices/ - Compressed files for cell-gene/bin-counts matrices of Adult Cerebral Cortex cells only. - Compressed files for cell-gene/bin-counts matrices of merged Fetal and Adult brain cells. - Metadata files of sequenced cells are inside the compressed files. - Cluster/Ident to Annotation information available from the GitHub page. Combined analysis of RNA and accessible chromatin in single-cells.