More recently, next-generation sequencing has enabled us to measure genome, transcriptome, and epigenome at the single-cell level at a resolution and scale previously impossible. However, challenges persist, particularly in understanding diseases and complex biological systems, since cells interact with each other within the tissue environment. The spatial organization of cells within tissues strongly influences their function, underscoring the importance of integrating spatial information into genomic studies. In recent years, significant advancements in high-throughput sequencing technologies, coupled with innovative spatial barcoding and fluorescence microscopy technologies, have paved the way for developing a suite of spatial transcriptome (ST) technologies to measure gene expression in situ. Current ST techniques have evolved rapidly in sensitivity, multiplexing, and throughput, and ST is emerging as a revolutionary genomic technology that bridges tissue and genomic measurements together tightly.
ST measures gene expression in specific locations within tissue samples. In ST, tissue sections or intact samples are spatially barcoded or indexed, correlating gene expression data with precise spatial coordinates. Spatially resolved gene expression data provide critical insights into the spatial heterogeneity of cell types, cell-cell interactions, molecular gradients within tissues, groups of spatially co-varying genes, and gene signatures associated with pathologic features. There are two main types of ST platforms: imaging (iST) and sequencing (sST) modalities. sST methods tag transcripts with oligonucleotide addresses indicating spatial location, typically by placing tissue slices on a barcoded substrate, isolating tagged transcripts for sequencing, and computationally mapping transcript identities to locations. iST methods use variations of fluorescence in situ hybridization (FISH), where mRNA molecules are tagged with hybridization probes and detected in a combinatorial manner over multiple rounds of staining with fluorescent reporters, imaging, and de-staining. Computational reconstruction then yields maps of transcript identity with single-molecule resolution. iST targets subsets of the transcriptome using pre-defined gene panels with higher spatial resolution and sensitivity than sST. As ST techniques continue to evolve, coupled with rapidly emerging computational and analytic methods, they are poised to become indispensable for dissecting the spatial complexity of biological systems at unprecedented resolution. These platforms show tremendous promise for translational research and diagnostic applications in cancer, neuroscience, and aging, aligning with the strengths of the UTHSA research community.
The GSF performs spatial transcriptomics analysis through the 10X Genomics CytAssist system. For spatial transcriptomics analysis, the GSF offers standard visium and visium HD services and provides library preparation and sequencing: 10xgenomics.com/platforms/visium. Visium HD reveals whole transcriptome analysis at a single-cell scale.