Spatially resolved single-cell genomics and transcriptomics by imaging

Abstract

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.

Fig. 1 |. Imaging-based single cell genomics and transcriptomics approaches.

a, A multiplex FISH scheme. For simplicity, a MERFISH scheme is used as an illustrative example. A binary barcoding scheme is shown together with how the barcodes are imprinted on the RNAs with a library of encoding probes and detected bit-by-bit with distinct readout probes. b, A simplified scheme for in situ sequencing. The nucleic acid sequence could either be the endogenous sequences of the genes or barcode sequences assigned to the genes, which are detected nucleotide-by-nucleotide via sequencing. Depending on the different sequencing chemistries used (not depicted here), the colors of the circles may indicate the identity of individual nucleotide or adjacent dinucleotide pairs.

Fig. 2 |. Three example application areas of imaging-based single-cell genomics and transcriptomics.

a, Cell atlas of complex tissues. A cell-type map of a region in the mouse hypothalamus is shown as an example, with different types of cells shown in different colors. b, Intracellular organization of the transcriptome. MERFISH image of >10,000 genes in individual cells is shown as an example, with RNA molecules from different genes shown in different colors. c, 3D organization of the genome. MERFISH image of >1,000 genomic loci (bottom) and transcription bursts of >1,000 genes (top) in a single nucleus is shown as an example.