Methods to map chromatin accessibility are used to probe the role of the chromatin landscape in shaping cellular states and how they can evolve. However, the methods generally require tissue dissociation, and most information about spatial context is lost. Writing in Nature, the labs of Rong Fan and Gonçalo Castelo-Branco now present spatial-ATAC-seq, a method for genome-wide mapping of chromatin accessibility in tissues with high-spatial cellular resolution. The Tn5 transposition step is performed on fixed tissue sections, with adapters containing a ligation linker inserted into accessible genomic loci. This is followed by two rounds of in situ ligation with DNA barcodes delivered using microchannels to define the spatial x–y coordinates of nuclei. Next, the tissues are imaged to correlate the spatially barcoded accessible chromatin with its morphology. Reverse crosslinking releases the barcoded DNA fragments to be amplified for library preparation.
By applying spatial-ATAC-seq to mouse embryos, the authors confirmed that the aggregate profiles obtained reproduce bulk measurements. Spatial chromatin-accessibility mapping of mouse embryos at embryonic days 11 and 13 identified tissue-specific signals that correlate with known patterns of developmental gene expression and traced chromatin dynamics during neural lineage differentiation. Next, the authors mapped mouse postnatal day 21 coronal and adult archival human coronal brain sections, and confirmed that spatial-ATAC-seq can spatially resolve many different cellular populations in these complex tissues. Pseudotime analysis further revealed the differentiation trajectory of these cells — for example, all the way from radial glia to excitatory neurons — that can be directly visualized in the tissue. Finally, mapping of human tonsil tissue identified distinct organization patterns of immune cells, lymphoid follicles and extrafollicular zones. This new method thus places chromatin mapping in the centre of the exciting field of spatial genomics, and enables further exploration of the role of chromatin dynamics in cell identity and fate decisions in development and disease.
This is a preview of subscription content, access via your institution