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

Chee-Huat Linus Eng, Michael Lawson, Qian Zhu, Ruben Dries, Noushin Koulena, Yodai Takei, Jina Yun, Christopher Cronin, Christoph Karp, Guo-Cheng Yuan and Long Cai ()
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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

Nature, 2019, vol. 568, issue 7751, 235-239

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-1049-y

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