Spatial transcriptomics is a method in biology that allows scientists to measure gene activity within tissues while preserving the location of cells. This approach provides a detailed map of messenger RNA (mRNA) transcripts in their original state within cells or tissues. NanoString Technologies has made this technology accessible to researchers. It enables exploration of mRNA transcripts, connecting gene expression patterns to their precise cellular location.
The Importance of Spatial Context
Understanding where gene activity occurs within a tissue is important for understanding both normal biological processes and disease progression. Traditional methods, such as bulk RNA sequencing, analyze gene expression from an entire tissue, averaging signals from diverse cell types and losing spatial information. Similarly, single-cell RNA sequencing isolates individual cells, which provides high-resolution gene expression data for each cell but disconnects them from their native tissue environment. These methods, while valuable, remove the spatial context that dictates how cells interact and function.
Cells within a tissue do not operate in isolation; their behavior is influenced by their neighbors and microenvironment. Cell-cell interactions, tissue architecture, and local environment all play a role in processes like tumor growth, the functioning of neurological circuits, and immune responses. For instance, understanding how cancer cells interact with immune cells or blood vessels within a tumor is difficult without knowing their spatial arrangement. Without this spatial information, many complex biological questions, particularly those involving cellular communication and tissue organization, cannot be fully answered.
How NanoString Platforms Work
NanoString’s platforms, such as the GeoMx Digital Spatial Profiler (DSP) and the CosMx Spatial Molecular Imager (SMI), allow researchers to analyze gene and protein expression directly within tissue sections, maintaining spatial coordinates. The GeoMx DSP system uses probes that bind to RNA or proteins in tissue samples. These probes are tagged with oligonucleotide barcodes linked by a UV-photocleavable linker. Researchers select regions of interest (ROIs) on the tissue, guided by fluorescently stained morphology markers.
Upon UV light exposure, barcodes are released from the selected ROIs and collected. These are then quantified using either the NanoString nCounter Analysis System or Next-Generation Sequencing (NGS). This process profiles hundreds of proteins or thousands of RNA transcripts from distinct tissue compartments or cell populations. The CosMx SMI is an imaging-based platform that uses cyclic in situ hybridization chemistry to quantify up to 6,000 RNA and 64 protein analytes at single-cell and subcellular resolution. It identifies the X, Y, and Z coordinates of each target molecule, enabling detailed spatial mapping. Both platforms combine imaging, molecular barcoding, and data analysis to map gene expression back to its origin within the tissue.
Transforming Biological Research
NanoString’s spatial transcriptomics technologies are significantly impacting various areas of biological and medical research. In oncology, these platforms help researchers decipher the complex tumor microenvironment by identifying the spatial distribution of different cell types, including malignant, stromal, and immune cells. This information can reveal biomarkers for predicting treatment response and provide insights into metastasis. For example, studies can observe how macrophages express more SPP1 in tumor interiors compared to immune-rich areas.
In neuroscience, spatial transcriptomics enables detailed mapping of cell types and gene expression patterns within the brain, which is important for understanding neurodegenerative diseases and complex neural networks. For immunology, the technology helps characterize immune cell infiltration and interactions within tissues during infections or autoimmune conditions, providing a clearer picture of the immune response in its native context. Developmental biology also benefits, as researchers can trace gene expression changes during organ development and differentiation, gaining insights into how tissues form and mature. This technology moves research beyond simply identifying genes to understanding where and how they function in their natural tissue environment, leading to new insights into disease mechanisms, potential therapeutic targets, and diagnostic tools.