A unified molecular approach for spatial epigenome, transcriptome, and cell lineages

Spatial epigenomics and multiomics can provide fine-grained insights into cell state but widespread adoption is limited by the requirement for bespoke slides and capture chemistries for each data modality. Here, we develop an approach (SPACE-seq) that uses a transposome with polyadenine adaptors to generate polyA-tailed epigenomic libraries, enabling facile spatial epigenomics and multiomics using standard whole transcriptome reagents. Application of SPACE-seq to a human glioblastoma specimen defines the spatial localization and accessible chromatin of distinct sub-populations within the tumor, and putative mitochondrial DNA variants. Overall design: Tissue sections from mouse brain were used to develop SPACE-seq, a genomics method that adapts the commercially available 10X Visium CytAssist v2 workflow to capture epigenomic data (spatial ATAC-seq) alongside spatial transcriptomics. SPACE-seq was then applied to a clinical human glioblastoma sample.