Navigating Life in Three Dimensions: An Introduction to Spatial Biology

Spatial biology is revolutionizing biomedical research by emphasizing the 3-dimensional relationships and arrangements of biological molecules within tissues and cells. This innovative field merges molecular biology with cutting-edge imaging technologies, unveiling the importance of not just molecular events, but also their precise locations. The insight that the ‘where’ matters as much as the ‘what’ marks a substantial shift in our approach to studying cellular organization and function. This blog post will delve into the technologies driving spatial biology forward, facilitating novel insights into the mechanisms that underlie health and disease.

1. Emergence of Spatial Technologies

Recent advancements in imaging technologies are one of the key factors paving the way for spatial biology to flourish. Tools such as transcriptomics, proteomics, and genomics become even more powerful when combined with an understanding of the spatial distribution of their data points. Traditional molecular assays are given additional context with knowledge of their placement within tissues and cells. In some cases, these technologies enable researchers to generate detailed maps of biological landscapes. For example, in their 2018 Science paper “Multiplexed protein maps link subcellular organization to cellular states,” Gut et al. demonstrate the creation of complex readouts providing quantitative support for metabolic analysis at a single-cell level.

2. In Situ Sequencing

In situ sequencing is a specific landmark technology that enabled the growth of spatial biology. Rising to prominence with a ‘Nature Methods’ paper by Ke et al. in 2013 (In situ sequencing for RNA analysis in preserved tissue and cells”), this approach enables the direct sequencing of RNA within intact tissues. Results of this method provide a wealth of information about the spatial heterogeneity of gene expression patterns all the way down to point mutations, allowing researchers to dissect the intricate tapestry of cellular diversity.

3. Spatial Transcriptomics

Another landmark advancement in the history of spatial biology – spatial transcriptomics – fully emerged in 2016 with a publication in ‘Science’ by Ståhl et al. outlining a strategy for analysis of transcriptome data with regard to its location within tissue sections (“Visualization and analysis of gene expression in tissue sections by spatial transcriptomics”). This technique allows for the simultaneous visualization of multiple RNA molecules in tissues. By preserving the spatial context, researchers can unravel the complex interplay of gene expression within specific cellular neighborhoods.

4. Single Cell Profiling

The 2020s witnessed the integration of spatial biology with single-cell analysis. Such synergy allows researchers to explore the spatial organization of individual cells within tissues, describing

biological heterogeneity in unprecedented detail. This approach applies not only to the application of molecular assays to single-cell samples, but also to precise image analysis made possible by data processing pipelines designed to provide resolution at the scale of individual cells. For example, see the previous Visikol blog post “Insights of Cell Segmentation in Cell Painting Image Analysis” for a discussion of the significance of cell segmentation for proper evaluation of images acquired via cell painting.

Spatial biology will continue to reshape biomedical research by unveiling detailed insights into the progression and operation of diseases such as cancer, neurodegenerative disorders, and autoimmune conditions. Additionally, it enhances neurobiology by charting the brain’s intricate networks, significantly influencing our grasp of brain function, development, and disorders. This shift from traditional molecular research to exploring the spatial architecture of biological systems introduces a new dimension to our understanding, promising to unlock cellular organization’s mysteries and redefine disease research. As we navigate this groundbreaking field, we invite you to join us in exploring the potential of spatial biology with Visikol’s in vitro models, paving the way for transformative discoveries in the biological sciences. Please reach out to a member of our team to get started today.

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