Whole-organ spatial transcriptional analysis at cellular resolution using TRISCO.

TRISCO enables single-cell 3D RNA mapping in cleared mouse organs, including brain, lung, heart, kidney, and spinal cord, with whole-tissue homogeneous in situ hybridization signal retention.

• Why it matters: Whole-organ 3D histology needs transcript imaging in intact organs, but existing approaches for RNA visualization are limited compared with protein-focused methods.
• What they did: The protocol uses Tris buffer-mediated retention of in situ hybridization chain reaction signal, producing cellular-resolution 3D transcript maps across tissue volumes.
• The result: TRISCO has been applied to multiple mouse organs and also to rat and guinea pig brains, with a workflow that takes 10–15 days and includes flexible stopping points.

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