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bioRxiv · 10.1101/2021.01.25.427807

Seq-Scope: Submicrometer-resolution spatial transcriptomics for single cell and subcellular studies

Cho, C.-S.·Xi, J.·Park, S.-R.·Hsu, J.-E.·Kim, M.·Jun, G.·Kang, H. M.·Lee, J. H.
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Abstract

Spatial barcoding technologies have the potential to reveal histological details of transcriptomic profiles; however, they are currently limited by their low resolution. Here we report Seq-Scope, a spatial barcoding technology with a resolution almost comparable to an optical microscope. Seq-Scope is based on a solid-phase amplification of randomly barcoded single-molecule oligonucleotides using an Illumina sequencing-by-synthesis platform. The resulting clusters annotated with spatial coordinates are processed to expose RNA-capture moiety. These RNA-capturing barcoded clusters define the pixels of Seq-Scope that are approximately 0.5-1 m apart from each other. From tissue sections, Seq-Scope visualizes spatial transcriptome heterogeneity at multiple histological scales, including tissue zonation according to the portal-central (liver), crypt-surface (colon) and inflammation-fibrosis (injured liver) axes, cellular components including single cell types and subtypes, and subcellular architectures of nucleus, cytoplasm and mitochondria. Seq-scope is quick, straightforward and easy-to-implement, and makes spatial single cell analysis accessible to a wide group of biomedical researchers.

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Cho, C.-S., Xi, J., Park, S.-R., Hsu, J.-E., Kim, M., Jun, G., Kang, H. M., Lee, J. H.. 2021-01-27. Seq-Scope: Submicrometer-resolution spatial transcriptomics for single cell and subcellular studies. https://doi.org/10.1101/2021.01.25.427807

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