Spatial Transcriptomics: Biotechnologies, Computational Tools, and Neuroscience Applications

Abstract Spatial transcriptomics (ST) represents a revolutionary approach in molecular biology, providing unprecedented insights into the spatial organization of gene expression within tissues. This review aims to elucidate advancements in ST technologies, their computational tools, and their pivotal applications in neuroscience. It is begun with a historical overview, tracing the evolution from early image‐based techniques to contemporary sequence‐based methods. Subsequently, the computational methods essential for ST data analysis, including preprocessing, cell type annotation, spatial clustering, detection of spatially variable genes, cell–cell interaction analysis, and 3D multi‐slices integration are discussed. The central focus of this review is the application of ST in neuroscience, where it has significantly contributed to understanding the brain's complexity. Through ST, researchers advance brain atlas projects, gain insights into brain development, and explore neuroimmune dysfunctions, particularly in brain tumors. Additionally, ST enhances understanding of neuronal vulnerability in neurodegenerative diseases like Alzheimer's and neuropsychiatric disorders such as schizophrenia. In conclusion, while ST has already profoundly impacted neuroscience, challenges remain issues such as enhancing sequencing technologies and developing robust computational tools. This review underscores the transformative potential of ST in neuroscience, paving the way for new therapeutic insights and advancements in brain research.