Tracing colonic embryonic transcriptional profiles and their reactivation upon intestinal damage

We lack a holistic understanding of the genetic programs orchestrating embryonic colon morphogenesis and governing damage response in the adult. A window into these programs is the transcriptomes of the epithelial and mesenchymal cell populations in the colon. Performing unbiased single-cell transcriptomic analyses of the developing mouse colon at different embryonic stages (embryonic day 14.5 [E14.5], E15.5, and E18.5), we capture cellular and molecular profiles of the stages before, during, and after the appearance of crypt structures, as well as in a model of adult colitis. The data suggest most adult lineages are established by E18.5. We find embryonic-specific gene expression profiles and cell populations that reappear in response to tissue damage. Comparison of the datasets from mice and human colitis suggests the processes are conserved. In this study, we provide a comprehensive single-cell atlas of the developing mouse colon and evidence for the reactivation of embryonic genes in disease. [Display omitted] •Single-cell profiling shows most adult colon lineages are established in late development•Development and disease comparison depicts reactivation of embryonic programs•Reactivated embryonic programs in colitis are conserved in mouse and human Fazilaty et al. provide a comprehensive single-cell atlas of developing mouse colon and colitis. They show that systematic comparison of cell-molecular profiles of the colon during development and disease reveals important programs that are reactivated in colitis. This can lead to better understanding of key molecular pathways in colitis.