sci-Space – a new method for embryo-scale, single-cell spatial transcriptomics

Researchers from the University of Washington introduce “sci-Space,” a new approach to spatial transcriptomics that can retain single-cell resolution and spatial heterogeneity at scales much larger than previous methods. They used their approach to build single-cell atlases of whole sections of mouse embryos at 14 days of development.

Single-cell RNA sequencing methods have led to great advances in understanding how organisms and complex tissues develop. Although cells’ spatial organization is central to normal development, homeostasis, and pathophysiology, many single-cell RNA sequencing methods lose valuable contextual spatial information. Those that preserve spatial context between cells can be limited to a specific set of genes and/or a small tissue area.

To overcome these challenges, Sanjay Srivatsan and colleagues developed sci-Space, a spatial transcriptomic approach that retains single-cell resolution while also resolving spatial context of cells at larger scales. Their approach uses a grid of barcoded oligos – short, single strands of synthetic DNA – that can be transferred from a slide to nuclei of an overlaid frozen tissue section. According to the authors, sci-Space allows for both the spatial origin and transcriptome for thousands of cells per slide to be obtained. To demonstrate their new technique, the researchers applied sci-Space to developing mouse embryos. By capturing spatial coordinates and whole transcriptomes of nearly 120,000 cells, the authors assembled a spatially resolved single-cell atlas of whole day 14 mouse embryo sections and revealed spatially expressed genes across a variety of cell types, including differentiating neurons.

Srivatsan SR, Regier MC, Barkan E, Franks JM, Packer JS, Grosjean P, Duran M, Saxton S, Ladd JJ, Spielmann M, Lois C, Lampe PD, Shendure J, Stevens KR, Trapnell C. (2021) Embryo-scale, single-cell spatial transcriptomics. Science 373(6550):111-117. [abstract]

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