Chromatin accessibility and RNA expression in E14.5 mouse neurons

The differential activity of transcription factors (TFs) manifests in a differential genome activation in different cell lineages and cell types. Here, we have mapped mRNA expression and accessible chromatin regions in single cells derived from the developing mouse CNS. We first defined a reference set of features for scATAC-seq read quantitation across samples, allowing comparison of chromatin accessibility between brain regions and cell types directly. Second, we integrated the scRNA and scATAC data to form a unified resource of transcriptome and chromatin accessibility landscape for the cell types in diencephalon to anterior hindbrain in E14.5 mouse embryo. We show that both the chromatin accessibility and transcriptome can be used as basis for clustering and cell type definition, with high concordance. Hierarchical clustering by the similarity in genome activation reveals complex interrelationships between the cell types derived from different anteroposterior domains of the E14.5 CNS. Further work is required to describe the fraction of genome activation resulting from the activity of patterning genes and the fraction activated by the cell fate selection regulators.