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High-definition spatial transcriptomics for in situ tissue profiling.

ABSTRACT: Spatial and molecular characteristics determine tissue function, yet high-resolution methods to capture both concurrently are lacking. Here, we developed high-definition spatial transcriptomics, which captures RNA from histological tissue sections on a dense, spatially barcoded bead array. Each experiment recovers several hundred thousand transcript-coupled spatial barcodes at 2-?m resolution, as demonstrated in mouse brain and primary breast cancer. This opens the way to high-resolution spatial analysis of cells and tissues.

SUBMITTER: Vickovic S

PROVIDER: S-EPMC6765407 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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High-definition spatial transcriptomics for in situ tissue profiling.

Vickovic Sanja S Eraslan Gökcen G Salmén Fredrik F Klughammer Johanna J Stenbeck Linnea L Schapiro Denis D Äijö Tarmo T Bonneau Richard R Bergenstråhle Ludvig L Navarro José Fernandéz JF Gould Joshua J Griffin Gabriel K GK Borg Åke Å Ronaghi Mostafa M Frisén Jonas J Lundeberg Joakim J Regev Aviv A Ståhl Patrik L PL

Nature methods 20190909 10

Spatial and molecular characteristics determine tissue function, yet high-resolution methods to capture both concurrently are lacking. Here, we developed high-definition spatial transcriptomics, which captures RNA from histological tissue sections on a dense, spatially barcoded bead array. Each experiment recovers several hundred thousand transcript-coupled spatial barcodes at 2-μm resolution, as demonstrated in mouse brain and primary breast cancer. This opens the way to high-resolution spatial ...[more]

PMID: 31501547

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High-density spatial transcriptomics arrays for in situ tissue profiling

Project description:Tissue function relies on the precise spatial organization of cells characterized by distinct molecular profiles. Single-cell RNA-Seq captures molecular profiles but not spatial organization. Conversely, spatial profiling assays to date have lacked global transcriptome information, throughput or single-cell resolution. Here, we develop High-Density Spatial Transcriptomics (HDST), a method for RNA-Seq at high spatial resolution. Spatially barcoded reverse transcription oligonucleotides are coupled to beads that are randomly deposited into tightly packed individual microsized wells on a slide. The position of each bead is decoded with sequential hybridization using complementary oligonucleotides providing a unique bead-specific spatial address. We then capture, and spatially in situ barcode, RNA from the histological tissue sections placed on the HDST array. HDST recovers hundreds of thousands of transcript-coupled spatial barcodes per experiment at 2 μm resolution. We demonstrate HDST in the mouse brain, use it to resolve spatial expression patterns and cell types, and show how to combine it with histological stains to relate expression patterns to tissue architecture and anatomy. HDST opens the way to spatial analysis of tissues at high resolution.

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High-density spatial transcriptomics arrays for in situ tissue profiling

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