Tracing colonic embryonic transcriptional profiles and their reactivation upon intestinal damage

Cell Rep. 2021 Aug 3;36(5):109484. doi: 10.1016/j.celrep.2021.109484.

Abstract

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.

Keywords: DSS; Single cell RNA sequencing; colitis; colon development; colon inflammatory disease; hindgut development; intestinal damage; intestinal development; single-cell atlas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Colitis / genetics
  • Colon / embryology*
  • Colon / pathology*
  • Disease Models, Animal
  • Embryo, Mammalian / metabolism
  • Gene Expression Profiling*
  • Gene Expression Regulation, Developmental
  • Humans
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / embryology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Mesoderm / embryology
  • Mice
  • Mice, Inbred C57BL
  • Single-Cell Analysis