The promise of spatial transcriptomics for neuroscience in the era of molecular cell typing

Abstract

The stereotyped spatial architecture of the brain is both beautiful and fundamentally related to its function, extending from gross morphology to individual neuron types, where soma position, dendritic architecture, and axonal projections determine their roles in functional circuitry. Our understanding of the cell types that make up the brain is rapidly accelerating, driven in particular by recent advances in single-cell transcriptomics. However, understanding brain function, development, and disease will require linking molecular cell types to morphological, physiological, and behavioral correlates. Emerging spatially resolved transcriptomic methods promise to fill this gap by localizing molecularly defined cell types in tissues, with simultaneous detection of morphology, activity, or connectivity. Here, we review the requirements for spatial transcriptomic methods toward these goals, consider the challenges ahead, and describe promising applications.