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Spatially resolved single-cell genomics and transcriptomics by imaging

Nature Methods volume 18, pages 18–22 (2021)Cite this article

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The recent advent of genome-scale imaging has enabled single-cell omics analysis in a spatially resolved manner in intact cells and tissues. These advances allow gene expression profiling of individual cells, and hence in situ identification and spatial mapping of cell types, in complex tissues. The high spatial resolution of these approaches further allows determination of the spatial organizations of the genome and transcriptome inside cells, both of which are key regulatory mechanisms for gene expression.

Humans, as well as many other organisms, are comprised of different types of cells. Yet the cell type composition and organization are still largely unknown for most organisms. The number of cell types could be vast. For instance, a mammalian brain could contain hundreds to thousands of different types of cells. Single-cell transcriptomic profiling provides a systematic and quantitative approach to identify cell types and determine their composition in tissues. However, when cells are dissociated from tissues for sequencing analysis, their spatial context is lost. Yet the spatial organization of cells is critical for tissue function. Furthermore, inside cells, the genomic DNA is folded into complex three-dimensional (3D) structures, which are vital to gene expression regulation. Likewise, intracellular organization of RNAs provides an important post-transcriptional regulatory mechanism. Thus, high-resolution, spatially resolved single-cell omics analysis is critically needed.

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Fig. 1: Imaging-based single cell genomics and transcriptomics approaches.
Fig. 2: Three example application areas of imaging-based single-cell genomics and transcriptomics.

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Acknowledgements

I am grateful to J. Moffitt for suggestions and comments on the paper, and to J. Moffitt, B. Bintu and J. Fan for help with figures. This work is supported in part by the National Institutes of Health. X.Z. is a Howard Hughes Medical Institute investigator.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Cambridge, MA, USA

    Xiaowei Zhuang

  2. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA

    Xiaowei Zhuang

  3. Department of Physics, Harvard University, Cambridge, MA, USA

    Xiaowei Zhuang

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Correspondence to Xiaowei Zhuang.

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X.Z. is a cofounder and consultant of Vizgen and an inventor on patents applied for by Harvard University related to MERFISH.

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Zhuang, X. Spatially resolved single-cell genomics and transcriptomics by imaging. Nat Methods 18, 18–22 (2021). https://doi.org/10.1038/s41592-020-01037-8

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