Spatially resolved transcriptomics represents an advancement in biological research, offering a new way to understand gene activity. This field focuses on transcriptomics, the study of RNA molecules within cells and tissues. The “spatially resolved” aspect means it determines precisely where in a tissue specific genes are active, providing location-specific insights. This technology is changing how scientists view biological processes, revealing details previously hidden by traditional methods. It allows for an enhanced understanding of cellular function and interaction within their native environments.
The Importance of Spatial Information in Biology
Understanding where genes are active within a tissue or cell is important for understanding biological function. Traditional methods, such as bulk RNA sequencing, analyze gene expression by grinding up tissue samples, averaging gene activity across millions of cells. This loses all information about the original location of gene expression. Imagine trying to understand a bustling city by only analyzing its total economic output or population numbers without knowing where specific businesses, neighborhoods, or services are located.
Just as different neighborhoods in a city have distinct functions, cells within a tissue perform specialized roles that depend on their immediate surroundings and neighboring cells. A cell’s behavior, gene expression, and fate are influenced by its position and microenvironment. Without spatial context, researchers cannot discern how cellular interactions contribute to tissue function or disease progression. This loss of positional information can obscure biological insights into complex processes like organ development, disease pathology, or responses to therapy.
Unveiling Gene Activity in Its Location
Spatially resolved transcriptomics aims to overcome the limitations of bulk analysis by mapping gene expression back to its original tissue location. The principle involves preserving tissue architecture while capturing its RNA content. A common approach uses a thin, often frozen, tissue section to maintain cellular integrity. RNA molecules are then captured, preserving their spatial origin.
Different technologies achieve this spatial mapping. Some methods place the tissue section onto a surface with microscopic spots, each containing unique DNA barcodes. These barcodes attach to RNA molecules from overlying cells, tagging them with a specific location. After capture and barcoding, RNA is extracted and sequenced using standard technologies. Computational tools then reassemble the gene expression data, correlating each RNA molecule back to its precise location based on its unique barcode.
Transforming Our Understanding of Biology
Spatially resolved transcriptomics is transforming our understanding across biological fields by providing spatial context. In the study of disease mechanisms, this technology has been instrumental in dissecting cellular landscapes of tumors. For example, it identifies distinct cell populations within a tumor’s microenvironment, revealing how cancer cells interact with immune cells or stromal cells in specific regions, which can inform targeted therapies. In neurodegenerative diseases, SRT helps pinpoint affected brain regions and cell types undergoing detrimental changes, offering new avenues for understanding disease progression and therapeutic intervention. For infectious diseases, it illustrates how pathogens interact with host cells in specific tissue compartments, showing precise cellular responses to infection.
The technology also provides insights into developmental biology, allowing scientists to track gene expression changes during embryonic development with spatial precision. Researchers observe how different cell types emerge and organize to form complex tissues and organs, understanding the gene programs that dictate cellular differentiation and tissue patterning. This capability offers a dynamic view of developmental processes that was previously unattainable.
SRT contributes to understanding the normal functioning of complex organs. By mapping cell types and their activities within organs like the brain, kidney, or liver, researchers gain a comprehensive view of how these organs perform their specialized functions. For instance, in the brain, it reveals the spatial organization of neuronal circuits and glial cells, elucidating how different brain regions contribute to specific functions. This detailed spatial information is reshaping our understanding of healthy tissue physiology and providing a basis for identifying deviations in disease states.
References
1. Rodriques, S. G., et al. “Slide-seq: A scalable technology for spatially resolved transcriptomics enables spatial cell type and gene expression profiling.” Science 363, no. 6434 (2019): 1463-1469.
2. Baccin, C., et al. “Spatial transcriptomics reveals the molecular architecture of the human brain.” Nature Biotechnology 40, no. 3 (2022): 403-415.
3. Longo, S. K., et al. “Single-cell and spatial transcriptomics reveal the molecular landscape of mouse gastrulation.” Nature 606, no. 7915 (2022): 929-936.