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Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH+

Author

Listed:
  • Chee-Huat Linus Eng

    (California Institute of Technology)

  • Michael Lawson

    (California Institute of Technology)

  • Qian Zhu

    (Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health)

  • Ruben Dries

    (Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health)

  • Noushin Koulena

    (California Institute of Technology)

  • Yodai Takei

    (California Institute of Technology)

  • Jina Yun

    (California Institute of Technology)

  • Christopher Cronin

    (California Institute of Technology)

  • Christoph Karp

    (California Institute of Technology)

  • Guo-Cheng Yuan

    (Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health)

  • Long Cai

    (California Institute of Technology)

Abstract

Imaging the transcriptome in situ with high accuracy has been a major challenge in single-cell biology, which is particularly hindered by the limits of optical resolution and the density of transcripts in single cells1–5. Here we demonstrate an evolution of sequential fluorescence in situ hybridization (seqFISH+). We show that seqFISH+ can image mRNAs for 10,000 genes in single cells—with high accuracy and sub-diffraction-limit resolution—in the cortex, subventricular zone and olfactory bulb of mouse brain, using a standard confocal microscope. The transcriptome-level profiling of seqFISH+ allows unbiased identification of cell classes and their spatial organization in tissues. In addition, seqFISH+ reveals subcellular mRNA localization patterns in cells and ligand–receptor pairs across neighbouring cells. This technology demonstrates the ability to generate spatial cell atlases and to perform discovery-driven studies of biological processes in situ.

Suggested Citation

  • Chee-Huat Linus Eng & Michael Lawson & Qian Zhu & Ruben Dries & Noushin Koulena & Yodai Takei & Jina Yun & Christopher Cronin & Christoph Karp & Guo-Cheng Yuan & Long Cai, 2019. "Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH+," Nature, Nature, vol. 568(7751), pages 235-239, April.
    • Handle: RePEc:nat:nature:v:568:y:2019:i:7751:d:10.1038_s41586-019-1049-y
    DOI: 10.1038/s41586-019-1049-y
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