Spatial transcriptomics: paving the way for tissue-level systems biology

• Cells in tissues operate in structured microenvironments.
• Studying division of labor in tissues requires spatially-resolved transcriptomics.
• This is enabled by highly multiplexed smFISH, in-situ sequencing and tissue reference maps.
• Theory from engineering and ecology will uncover design principles of tissue organization.

The tissues in our bodies are complex systems composed of diverse cell types that often interact in highly structured repeating anatomical units. External gradients of morphogens, directional blood flow, as well as the secretion and absorption of materials by cells generate distinct microenvironments at different tissue coordinates. Such spatial heterogeneity enables optimized function through division of labor among cells. Unraveling the design principles that govern this spatial division of labor requires techniques to quantify the entire transcriptomes of cells while accounting for their spatial coordinates. In this review we describe how recent advances in spatial transcriptomics open the way for tissue-level systems biology.