Microscopic examination of spatial transcriptome using Seq-Scope

Cell. 2021 Jun 24;184(13):3559-3572.e22. doi: 10.1016/j.cell.2021.05.010. Epub 2021 Jun 10.

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 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.

Keywords: RNA capture; Spatial transcriptomics; colon; high resolution; histology; liver; molecular barcoding; scRNA-seq; spatial single cell analysis; subcellular analysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / genetics
  • Colon / pathology
  • Gene Expression Regulation
  • Hepatocytes / metabolism
  • Inflammation / genetics
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy*
  • Mitochondria / genetics
  • RNA / metabolism
  • Single-Cell Analysis
  • Transcriptome / genetics*

Substances

  • RNA