Light-Seq: Spatially targeted profiling of transcriptomic states in cells and tissue

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Summary We will develop a new spatial-omics platform, Light-Seq, for spatial indexing of intact biological samples using light-directed DNA barcoding in fixed cells and tissues followed by ex situ sequencing. Our light-directed barcoding strategy will enable user-directed, in situ selection of rare, disjoint cell populations for full- transcriptome sequencing based on morphology, location, or protein expression without dissociation. We will develop Light-Seq as a spatial-omic DNA barcoding platform capable of extracting the transcriptomic information from single-cells, scalable to uniquely address thousands of user-defined regions, and can be applied in both fixed and FFPE clinical samples for direct applications in human health. We envision that the Light-Seq platform will be a scalable, cost-effective, and flexible approach to spatial transcriptomics that allows the user to define spatial regions in tissue for NGS sequencing. Light-seq can thus serve as a low barrier-to-entry platform for spatial transcriptomics for many pathologists and researchers, and would be a key driver for a wider adoption of spatial transcriptomic tools.