Project description:We applied a combinatorial indexing assay, sci-ATAC-seq, to profile genome-wide chromatin accessibility in ~100,000 single cells from 13 adult mouse tissues. We identify 85 distinct patterns of chromatin accessibility, most of which can be assigned to cell types, and ~400,000 differentially accessible elements. We use these data to link regulatory elements to their target genes, to define the transcription factor grammar specifying each cell type, and to discover in vivo correlates of heterogeneity in accessibility within cell types. We develop a technique for mapping single cell gene expression data to single-cell chromatin accessibility data, facilitating the comparison of atlases. By intersecting mouse chromatin accessibility with human genome-wide association summary statistics, we identify cell-type-specific enrichments of the heritability signal for hundreds of complex traits. These data define the in vivo landscape of the regulatory genome for common mammalian cell types at single-cell resolution.
Project description:We applied a combinatorial indexing assay, sci-ATAC-seq, to profile genome-wide chromatin accessibility in ?100,000 single cells from 13 adult mouse tissues. We identify 85 distinct patterns of chromatin accessibility, most of which can be assigned to cell types, and ?400,000 differentially accessible elements. We use these data to link regulatory elements to their target genes, to define the transcription factor grammar specifying each cell type, and to discover in vivo correlates of heterogeneity in accessibility within cell types. We develop a technique for mapping single cell gene expression data to single-cell chromatin accessibility data, facilitating the comparison of atlases. By intersecting mouse chromatin accessibility with human genome-wide association summary statistics, we identify cell-type-specific enrichments of the heritability signal for hundreds of complex traits. These data define the in vivo landscape of the regulatory genome for common mammalian cell types at single-cell resolution.
Project description:Recent surveys of mouse organogenesis cell atlas (MOCA) with single cell transcriptomics have uncovered hundreds of cell types, but the cell-type-specific transcriptional regulatory programs responsible for the unique identity and function of each cell type have yet to be elucidated. We applied a four-level combinatorial indexing assay, SPATAC-seq, to profile the chromatin accessibility in >350,000 cells derived from 13 embryos staged between embryonic day (E) 10.5 and 13.5 in a single experiment. The resulting map revealed the status of open chromatin for 844,817 candidate cis-regulatory elements (cCREs) in 33 main cell types and 296 subtypes. By integrating this accessible chromatin atlas with scRNA data of MOCA, we characterized the gene regulatory sequences and transcription factors associated with cell fate commitment, such as unreported role of Nr5a2 and Gata6 in gastrointestinal tract. Finaly, we integrated this atlas with previous scATAC-seq data from mouse embryos at E8.25 and 13 adult mouse tissues to dissect life stage specific gene regulatory programs across different cell types. This rich resource and comprerhensive analysis provide a foundation for expolring gene regulators in mammalian cell differentiation.