Chrono-atlas of cell-type specific daily gene expression rhythms in the regenerating colon

The circadian clock is present throughout the body, including the intestine, where it regulates daily physiology through rhythmic gene expression. The large intestine (colon) is composed of many functionally distinct cell types; how daily rhythms in transcript abundance are coordinated in specific cells is not known. Using single-cell transcriptomics, we analyzed 24-hour gene expression rhythms in all major cell types of the colon following injury. Such rhythms are not uniformly distributed: rhythmic genes, including circadian clock components, clock targets, and systemic response programs, differ in their timing, and are cell-type-, region-, or injury- specific. Compared to stromal and muscle cells, which exhibit robust circadian clock rhythms, epithelial cells show weaker oscillations. During regeneration, cells of the epithelium, stroma, and immune system display strong biphasic rhythms in metabolic, protein processing, and temperature response genes, and epithelial clocks are reprogrammed to become 12-hours antiphasic in timing. Our data reveal unexpected complexity in the colon and provide a resource by identifying the cellular source of 24-hour transcript rhythms.