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Covering the Cover – Gastroenterology


Anal transitional zone squamous epithelial cells are an additional source of regenerative epithelium in mouse models of colitis.

Toxins, pathogens, mechanical injury, and inflammatory insult, such as occurring in inflammatory bowel disease, continuously challenge intestinal epithelial integrity. In response, the damage must first be contained, followed by proliferation of the uninjured adjacent epithelium, and last by differentiation to restore healthy function. The restorative epithelium is thought to derive from a tissue type similar to the damaged one, that is, intestinal columnar epithelium. In this issue of Gastroenterology, Liu et al explore the possibility that cells from another tissue type might repopulate damaged epithelium in colitis. Using dextran sodium sulfate to induce colitis in mice, they discovered that, after injury, the neoepithelium immediately proximal to the dentate line consisted of squamous, nonkeratinized cells, and they named this regenerative epithelium squamous neoepithelium of the colon (SNEC) (Figure 2). Similar observations were made in the IL-10–/– mouse model, indicating this was not unique to dextran sodium sulfate colitis. Lineage tracing determined that SNEC arose from anal transition zone cells. Single cell RNA sequencing analysis determined that these restorative cells are molecularly distinct squamous tissue executing colonic transcriptomic programs. After injury, transition zone cells adopt a progenitor state during SNEC development, at which time SNEC up-regulates colonic expression patterns, eventually yielding stem cells that regenerate a healthy crypt-like pattern. This intriguing study identifies a previously unrecognized pool of restorative epithelium that may represent an additional therapeutic target to promote recovery after intestinal injury.

Figure 2Graphical Abstract.

See page 1975.



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