Chrono-atlas of cell-type specific daily gene expression rhythms in the regenerating colon
How tissues maintain circadian rhythms during regeneration remains poorly understood. Here, the authors generate a 24-hour single-cell transcriptomic atlas of the regenerating mouse colon and show that cells dynamically
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, the researchers analyzed 24-hour gene expression rhythms in all major cell types of the colon following injury. The results showed that rhythmic genes, including circadian clock components, clock targets, and systemic response programs, differ in their timing, and are cell-type-, region-, or injury- specific. In contrast to stromal and muscle cells, which exhibit robust circadian clock rhythms, epithelial cells display weaker oscillations. During regeneration, cells of the epithelium, stroma, and immune system display strong biphasic rhythms in metabolic, protein processing, and temperature response genes. Notably, epithelial clocks are reprogrammed to become 12-hours antiphasic in timing. These findings reveal unexpected complexity in the colon and provide a resource by identifying the cellular source of 24-hour transcript rhythms. The study highlights the importance of considering cell-type specific daily gene expression rhythms in the context of tissue regeneration and highlights the need for further research to understand the mechanisms underlying these complex rhythms.