Improved cell-type identification and comprehensive mapping of regulatory features with spatial epigenomics 96-channel microfluidic platform.

Gene expression is subject to epigenetic regulation and is dependent upon cellular context. Spatial omics tools can provide insight into cellular context; however, development has centered on spatial transcriptomics and proteomics. Deterministic barcoding in tissue for spatial omics sequencing (DBiT-seq) was the first spatial epigenomics platform at the cellular level. Here we present a comparison of spatial epigenomic profiling on both 50-channel and 96-channel platforms. The new 96-channel microfluidics chip design greatly improved precision in cell typing and identification of regulatory elements by spatial-ATAC-seq. Spatial mapping reveals complexity of glial cell and neuronal localization within brain structures as well as cis-regulatory elements controlling cellular function. This technology streamlines spatial analysis of the epigenome and contributes a new layer of spatial omics to uncover the context dependent regulatory mechanisms underpinning development, disease, and normal cellular function.