Uncovering an Organ’s Molecular Architecture at Single-Cell Resolution by Spatially Resolved Transcriptomics

Abstract

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. In this review, we focus on 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.

Subcellular sequencing of single neurons reveals the dendritic transcriptome of GABAergic interneurons

“…This method would thus be inadequate to profile mRNAs within individual dendritic branches. Instead, emerging methods in spatial transcriptomics relying on in-situ hybridization are better equipped for such questions (Eng et al, 2019;Liao et al, 2020;Xia et al, 2019). In contrast to FISH-based transcriptomic techniques, however, our method is unbiased (does not rely on a predetermined set of transcripts), bypasses secondary structure that may limit accessibility for certain mRNAs in situ, and does not suffer from signal saturation of highly abundant transcripts.…”

From whole-mount to single-cell spatial assessment of gene expression in 3D

“…Several single-cell atlasing projects are endeavouring to develop these public resources which provide a valuable source of information for many model organisms including The Human Cell Atlas 85 and single-cell zebrafish transcriptome atlas 86 . Ultimately, spatially resolved transcriptomics will be paramount in adding spatial coordinates to these single-cell atlasing projects 87 .…”

Subcellular sequencing of single neurons reveals the dendritic transcriptome of GABAergic interneurons

“…This method would thus be inadequate to profile mRNAs within individual dendritic branches. Instead, emerging methods in spatial transcriptomics relying on in-situ hybridization are better equipped for such questions (Eng et al, 2019; Liao et al, 2020; Xia et al, 2019). In contrast to FISH-based transcriptomic techniques, however, our method is unbiased (does not rely on a pre-determined set of transcripts), bypasses secondary structure that may limit accessibility for certain mRNAs in situ, and does not suffer from signal saturation of highly abundant transcripts.…”