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.

Department of Gastroenterology and Hepatology University Hospital Zurich Rämistrasse 100 8091 Zurich Switzerland

Department of Molecular Life Sciences University of Zurich Winterthurerstrasse 190 8057 Zurich Switzerland

Department of Molecular Life Sciences University of Zurich Winterthurerstrasse 190 8057 Zurich Switzerland; Institute of Molecular Genetics of the ASCR v v i Vídeňská 1083 142 20 Prague 4 Czech Republic

Institute of Molecular Genetics of the ASCR v v i Vídeňská 1083 142 20 Prague 4 Czech Republic

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