Single-cell RNA-Seq profiling of the mouse anorectal junction before, during, and after acute colitis

We have identified a squamous epithelium that repairs the distal colon of mice after injury and colitis. Lineage tracing studies demonstrate that this squamous epithelium is derived from a small zone of transitional cells located at the squamocolumnar junction of the rectum and anus. To characterize the molecular properties of this junctional epithelium in homeostasis, colitis, and regeneration, we profiled the distal colon and anus of mice using single-cell RNA-Seq. We found that junctional cells in this transition zone express high levels of Krt7 and, at baseline, co-express markers of both colonic epithelium and squamous epithelium. These cells thus represent a specialized reserve epithelial population capable of striking plasticity in their generation of a hybrid tissue type to mediate colonic repair. Overall design: Wildtype C57Bl/6 mice were exposed to the DSS colitis model for 6 d. They were dissected and their anorectal junctions analyzed via single-cell RNA-Seq at experimental day (exp d) 0 (unchallenged mice), exp d 7 (highly colitic mice), and exp d 42 (recovered mice).