Comprehensive Mapping of Transcriptionally-active Enhancers During Murine Cardiogenesis at Single Cell Resolution

An in-depth understanding of the complex mechanisms that orchestrate normal embryonic heart development is required to disambiguate the origin of congenital heart disease. However, the epigenetic landscapes governing cell type-specific gene expression patterns during heart development at single cell resolution has yet to be revealed. Here we use simultaneous single cell RNA and assay for transposase accessible chromatin sequencing to construct a comprehensive multimodal map of embryonic murine heart development, profiling cell type- and timepoint-specific epigenetic regulatory elements as well as their gene targets. Furthermore, we compare these regulatory elements with published GWAS hits to map variants implicated in key developmental processes and clinical phenotypes to enhancers for genes that are actively transcribed during cardiac development. Taken together, our work provides a rich resource for the broader scientific community that empowers future studies in heart development and disease and offers a simple computational framework for integrating and profiling multiomic data in single cells.