Spatial omics is an emerging field of study that combines various molecular assays with spatial information to study how biological molecules are distributed within tissues and cells at high resolution. By mapping molecules like DNA, RNA, proteins or metabolites to their precise locations, it offers new insights into important biological functions and disease mechanisms.
History and Methods
The inception of spatial omics can be traced back to developments in fluorescence in situ hybridization (FISH) in the late 1980s which allowed visualization of specific DNA or RNA sequences within intact cells. Later, technologies like microarrays and next-generation sequencing enabled profiling of gene expression from discrete regions of tissues. Today, several methods have been developed under the umbrella of spatial omics including spatial transcriptomics, protein mass spectrometry imaging, and multiplexed ion beam imaging (MIBI).
Spatial transcriptomics relies on in situ sequencing or RNA readout from tissue sections immobilized on a slide. It offers spatially resolved profiles of RNA transcripts from specific areas without need for microdissection. Protein mass spectrometry imaging uses MALDI or SIMS to map protein abundances and post-translational modifications at subcellular resolution. MIBI utilizes noble gas ion beams to sequentially ablate and analyze biomolecules from thin tissue slices, yielding 3D molecular maps.
Applications in Neuroscience
The spatial organization of the brain is closely linked to its function, making neuroscience a prime application area for spatial omics. Studying gene expression patterns across brain regions and cell types has enhanced understanding of neurodevelopment, neuronal connectivity and disease mechanisms. For example, spatial transcriptomic profiling of post-mortem Alzheimer’s disease brains identified disease-related genes and revealed how their expression varies between cortical layers and cell subtypes.
Another study used multiplexed ion beam imaging to map over 80 proteins and peptides in rat brain slices. This revealed co-localization patterns of receptors, transporters and enzymes that provided novel insights into neurotransmission regulation. Going forward, high-resolution 3D protein mapping throughout entire brains could improve models of neural circuits and aid drug discovery for neurological disorders.
Understanding Cancer Heterogeneity
Cancer is known to exhibit substantial intra-tumoral heterogeneity, with different sub-clones harboring diverse molecular aberrations and drug sensitivities within the same tumor. Spatial analyses are crucial to delineate how variations in the tumor microenvironment sculpt this molecular diversity.
Spatial transcriptomics of breast cancer samples has helped uncover distinct gene expression patterns among epithelial, stromal and immune cell populations in different tumor regions. Interestingly, expression of certain immune checkpoint genes showed spatial correlations with specific tumor sub-clones. Other studies mapping protein biomarkers in situ further elucidated how gradients in oxygenation, nutrients and signaling factors shape heterogeneity in cancers like glioblastoma.
Going forward, routine use of spatial omics in cancer research and precision oncology holds promise. By mapping clinical samples at high resolution, it may help predict tumor evolution, track minimal residual disease and guide development of combination therapies tailored for each patient.
Applications in Developmental Biology
Understanding how coordinated gene regulation drives spatial patterning and cell fate decisions during embryonic development is a major theme in developmental biology. Spatial analyses are uniquely positioned to illuminate these processes.
For instance, spatial transcriptomics of early mouse embryos revealed region-specific expression programs that distinguish the 3 germ layers. It also identified gradients of signaling factors across tissues and pinpointed progenitor zones undergoing differentiation. Another study mapped over 500 protein abundances across fruit fly egg chambers, uncovering novel patterning mechanisms, transport pathways and post-transcriptional controls operating during oogenesis.
By zooming into live embryos or thin sections, future applications of higher-resolution spatial omics promise to capture dynamic gene activities with single-cell precision. This could mechanistically explain morphogen signaling, cell migration paths and how aberrations lead to congenital defects. Ultrasensitive protein imaging may also trace lineage relationships and fate mapping over developmental time.
spatial omics is revolutionizing our ability to interrogate biological systems with an anatomical context. By pinpointing where molecular events occur within complex tissues and organisms, it reveals new functional relationships and disease insights not evident from conventional bulk assays. Ongoing technological advances promise even higher multiplexing and more comprehensive coverage of biomolecules across scales. Widespread adoption of spatial omics methodologies will undoubtedly yield novel discoveries and transform our understanding of biology and medicine in the years to come.