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 comparable to an optical microscope. Seq-Scope
is based on a solid-phase amplification of randomly barcoded
single-molecule oligonucleotides using an Illumina sequencing 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 ∼0.5-0.8 μm 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 and cytoplasm. Seq-Scope
is quick, straightforward, precise, and easy-to-implement and makes spatial
single-cell analysis accessible to a wide group of biomedical researchers.
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