Spatial multi-omic profiling of non-autonomous transcriptomic and epigenomic responses to genetic perturbation

Perturb-Tags enables cellular-resolution spatial multi-omic profiling in intact human embryoid bodies, jointly measuring guide RNAs, gene expression, chromatin accessibility, and spatial position.

• Why it matters: Cell-autonomous CRISPR pooled screens are common, but in situ, cellular-resolution measurement has limited direct study of non-autonomous regulatory mechanisms.
• What they did: The method tags nuclei with spatial barcodes for pooled CRISPR screening, then profiles single nuclei for gene expression, CRISPR guide RNAs, chromatin accessibility, and coordinates.
• The result: In human embryoid bodies, ligand, receptor, and kinase knockdowns produce extensive distance- and microenvironment-dependent non-autonomous transcriptional and chromatin changes, and a graph neural network models combined perturbation effects across tissue.

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