UCLA

Understanding the physiology of complex systems like tissues and organs is likely impossible without detailed structural maps of the anatomy, especially in the context of perturbations. Spatial transcriptomic techniques like Multiplexed Error Robust Fluorescence In Situ Hybridization or MERFISH have ushered in methods that are capable of generating these detailed anatomical maps for small regions of interest. Existing work primarily focuses on technological development, and few if any have compared perturbed to wild-type conditions. Here we present three cases of increasing difficulty where MERFISH can be used to compare a perturbed state to wild type. Existing spatial transcriptomic approaches, including MERFISH, lack the scale necessary to generate anatomical maps of large tissues and whole organs. Here we present Dimensionally Reduced Fluorescence In Situ Hybridization or dredFISH which allows the generation of detailed anatomical maps at scales far exceeding existing other approaches. Together the fundamental shift towards comparing biological conditions as well as the technological improvements in scale will provide a wealth of detailed anatomical maps which should provide unique physiological insights which likely would have been missed.