Spatial Transcriptomics: Integrating Morphology and Molecular Mechanisms of Kidney Diseases

Abstract

The recent arrival of high-resolution spatial transcriptomics (ST) technologies is generating a veritable revolution in life sciences, enabling biomolecules to be measured in their native spatial context. By integrating morphology and molecular biology, ST technologies offer the potential of improving the understanding of tissue biology and disease and may also provide meaningful clinical insights. This review describes the main ST technologies currently available and the computational analysis for data interpretation and visualization, and illustrate their scientific and potential medical interest in the context of kidney disease. Finally, we discuss the perspectives and challenges of these booming new technologies.

Figure 1

Classification of spatial transcriptomics (ST) technologies. Schematic tree representation of the classification of the main ST technologies. ST technologies could be divided into two main groups: those based on RNA extraction/capture, referred as extraction-based technologies (EBTs), and those based on in situ or ex situ RNA analysis without RNA extraction/capture, referred as non–extraction-based technologies (NEBTs). EBTs will account for the major part of sequencing-based technologies, whereas NEBTs will account for the major part of imaging-based technologies. DSP, digital spatial profiling; FISSEQ, fluorescent in situ sequencing; HDST, high-definition ST; ISH, in situ hybridization; ISS, in situ sequencing; ROI, region of interest; scRNAseq, single-cell RNA sequencing; seq, sequencing.

Figure 2

Spatial barcoding- and sequencing-based technologies. Schematic representation of tissue processing, library preparation, sequencing, and visualization for spatial barcoding- and sequencing-based technologies. Tissue section (kidney) is placed on a special slide with barcoded spots. mRNA or RNA probes are then locally captured within each spot for library generation and sequencing. Example of data output from the Visium technology on a kidney of a healthy adult mouse. UMI, Unique Molecular Identifier.

Figure 3

In situ imaging-based technologies. Schematic representation of tissue processing, serial hybridization-detection rounds, and visualization for in situ imaging-based technologies. Tissue section (kidney) is placed on a special slide for the subsequent serial hybridization of RNA target–specific probes. Probes are then sequentially imaged to determine a specific molecular identifier. Example of data output from the Xenium technology on a kidney of a healthy adult mouse. FISH, fluorescence in situ hybridization. RCA, rolling circle amplification.