Single-cell RNA-seq has one major drawback: since cells are isolated as a single-cell suspension from the source tissue, spatial context is lost. Recently, several solutions have been proposed, collectively called ‘spatial transcriptomics’. Here, we show that a standard single-cell RNA seq protocol can be applied to laser capture microdissected material. By sampling a tissue slice systematically (in a grid), a spatial transcriptome image can be built. In contrast to other recently proposed methods (e.g. FISSEQ), our approach requires only standard generally-available instruments.

We applied this technique to the embryonic medial ganglionic eminence, a brain structure that gives birth to a variety cortical interneurons. We were able to detect a transcriptome gradient across this structure ranging from the proliferative ventricular zone to the post-mitotic and migratory mantle zone. The technique should be a useful complement to single-cell RNA-seq. When used in combination, these techniques can provide both single-cell resolution and spatial context.

Topographical transcriptome mapping of the mouse medial ganglionic eminence by spatially-resolved RNA-seq
Published in Genome Biology (PDF)