Simultaneous profiling of spatial gene expression and chromatin accessibility during mouse brain development

Abstract

The brain is a complex tissue whose function relies on coordinated anatomical and molecular features. However, the molecular annotation of the spatial organization of the brain is currently insufficient. Here, we describe microfluidic indexing-based spatial assay for transposase-accessible chromatin and RNA-sequencing (MISAR-seq), a method for spatially resolved joint profiling of chromatin accessibility and gene expression. By applying MISAR-seq to the developing mouse brain, we study tissue organization and spatiotemporal regulatory logics during mouse brain development. MISAR-seq combines spatial-ATAC-seq and RNA-seq for spatial profiling of both chromatin accessibility and gene expression, as demonstrated in the developing mouse brain.