Uncovering an organ’s molecular architecture at single-cell resolution by spatially resolved transcriptomics

Revealing fine-scale cellular heterogeneity among spatial context and the functional and structural foundations of tissue architecture is fundamental within biological research and pharmacology. Unlike traditional approaches involving single molecules or bulk omics, cutting-edge, spatially resolved transcriptomics techniques offer near-single-cell or even subcellular resolution within tissues. Massive information across higher dimensions along with position-coordinating labels can better map the whole 3D transcriptional landscape of tissues. Researchers from Zhejiang University and the University of Sydney discuss developments and strategies in spatially resolved transcriptomics, compare the cell and gene throughput and spatial resolution in detail for existing methods, and highlight the enormous potential in biomedical research.

Throughput of Genes and Cells for Each Spatially Resolved Transcriptomics Method

Approaches are presented in different shapes, symbols, and sizes according to their categories (diamonds: in silico methods for spatial reconstruction; purple circles: spatial labeling methods; orange circles with a dashed border: LCM-based methods; orange circles with a solid border: MAPseq; blue circles with a solid border: image-based targeted methods; blue circles with a dashed border: Image-based untargeted methods). Distinct symbols donate the spatial resolution of each method (orange cell: cellular resolution; blue cell with shinning dots: subcellular resolution; multiple cells: regional resolution). The size of each symbol is related to its spatial resolution roughly. The x and y axes represent the number of measured cells or spots per handle and the actual genes determined in their experiments, respectively. Abbreviations: ExFISH, expansion FISH; FISH, fluorescence in situ hybridization; FISSEQ, fluorescence in situ sequencing; GEO-seq, geographical position sequencing; HDST, high-definition spatial transcriptomics; ISS, in situ sequencing; LCM, laser capture microdissection; MERFISH, multiplexed error-robust FISH; MAPseq, multiplexed analysis of projections by sequencing; osmFISH, ouroboros single-molecule FISH; PLISH, proximity ligation in situ hybridization; secFISH, sequential FISH; smHCR, single-molecule hybridization chain reaction; SRM, super resolution microscopy; STARmap, spatially-resolved transcript amplicon readout mapping; TIVA, transcriptome in vivo analysis; TSCS, topographic single-cell sequencing.