Photolabile oligonucleotides with topological light gradients enable spatially resolved single-cell transcriptomics and epigenomics.

We introduce scSTAMP-seq (single-cell spatial transcriptomic and multiomic profiling), a modular light-encoded barcoding strategy that preserves spatial information while leveraging standard single-cell platforms. scSTAMP-seq labels live and fixed cells with cholesterol-conjugated, photocleavable hashtag oligonucleotides, followed by patterned light exposure that 'stamps' spatial coordinates onto individual cells before single-cell multiome sequencing. Here we apply scSTAMP-seq to human embryoids showing how spatial organization and epigenetic states coregulate cellular programs in heterogeneous biological systems.