A human atlas of chromatin accessibility during development
To generate a human cell atlas of chromatin accessibility using tissues obtained during development, we devised an improved assay for single cell profiling of chromatin accessibility based on three-level combinatorial indexing (sci-ATAC-seq3). We applied this method to 53 fetal tissue samples representing 15 organs, altogether profiling on the order of one million single cells. We leveraged cell types defined by gene expression in the same organs to annotate these data, and then built a catalog of hundreds-of-thousands of candidate gene regulatory elements exhibiting cell type-specific accessibility. This resource allows, for example, the identification of lineage-specific transcription factors, prediction of cis-regulatory interactions based on co-accessibility or calculation of cell type-specific enrichments of complex trait heritability. Together with the companion human cell atlas of gene expression during development, these data comprise a rich resource for the exploration of human biology.