Space: the final frontier – CUT&Tag has just voyaged where no next-generation sequencing method has gone before to bring forth spatially-resolved histone modification profiles of intact mouse tissues! An expeditionary force led by Rong Fan (Yale University) combined in situ cleavage under targets and tagmentation (CUT&Tag) chemistry, microfluidic deterministic barcoding, and next-generation sequencing to develop Spatial-CUT&Tag.
Let’s hear how Deng and colleagues materialized Spatial-CUT&Tag and resolved spatially-distinct/cell-type-specific histone modifications during embryonic organogenesis and in the post-natal brain:
- Spatial-CUT&Tag demonstrates known histone modifications associations at repressed loci (H3K27me3) and activate enhancers/promoters (H3K4me3 and H3K27ac) in intact tissues of the developing mouse embryo, which gave spatially distinct chromatin states that identify similar cell types to tissue histology
- Comparing Spatial-CUT&Tag against ENCODE’s organ-specific ChIP-seq also provides good concordance
- Analysis of spatial patterning during embryonic development via cell-type-specific marker genes demonstrates how the absence of H3K27me3 and presence of H3K4me3/H3K27ac associates with heart-specific gene expression
- Additional correlation of single-cell transcriptomics with H3K27ac data predicts gene-enhancer interactions
- Spatial-CUT&Tag data integrates well with single-cell transcriptomics to identify organ-specific cell types in the embryo
- Examples include the enrichment of definitive erythroid lineage cells in the liver (a major hematopoietic organ during embryogenesis) and the presence of cardiac muscle cell types in the heart
- Spatial-CUT&Tag analysis of brain tissue also enables the evaluation of epigenetic processes controlling neurodevelopment
- H3K27me3 spatial analysis alone distinguishes major cell types from distinct layers of the developing mouse brain
- Integration of Spatial-CUT&Tag data with scRNA-seq/scCUT&Tag enables the prediction of the region that a specific cell-type from scRNA-seq or scCUT&Tag localizes to
Overall, this astronomically-awesome new next-generation sequencing-based method allows the spatial profiling of histone modifications in tissues, which will support studies into epigenetic regulation, cell function, and fate decisions in normal and disease conditions. The authors also mention that future upgrades, such as using a serpentine microfluidic channel or increasing the number of barcodes, may increase the extent of mapping.
Launch yourself over to this study in Science, February 2022.