| First Author | Jiang M | Year | 2017 |
| Journal | Nature | Volume | 550 |
| Issue | 7677 | Pages | 529-533 |
| PubMed ID | 29019984 | Mgi Jnum | J:252735 |
| Mgi Id | MGI:6098832 | Doi | 10.1038/nature24269 |
| Citation | Jiang M, et al. (2017) Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus. Nature 550(7677):529-533 |
| abstractText | In several organ systems, the transitional zone between different types of epithelium is a hotspot for pre-neoplastic metaplasia and malignancy, but the cells of origin for these metaplastic epithelia and subsequent malignancies remain unknown. In the case of Barrett's oesophagus, intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells. On the basis of a number of experimental models, several alternative cell types have been proposed as the source of this metaplasia but in all cases the evidence is inconclusive: no model completely mimics Barrett's oesophagus in terms of the presence of intestinal goblet cells. Here we describe a transitional columnar epithelium with distinct basal progenitor cells (p63(+)KRT5(+)KRT7(+)) at the squamous-columnar junction of the upper gastrointestinal tract in a mouse model. We use multiple models and lineage tracing strategies to show that this squamous-columnar junction basal cell population serves as a source of progenitors for the transitional epithelium. On ectopic expression of CDX2, these transitional basal progenitors differentiate into intestinal-like epithelium (including goblet cells) and thereby reproduce Barrett's metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues (including the anorectal junction) as well as in the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (believed to be a precursor of Barrett's oesophagus) are both characterized by the expansion of the transitional basal progenitor cells. Our findings reveal a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63(+)KRT5(+)KRT7(+) basal cells in this zone are the cells of origin for multi-layered epithelium and Barrett's oesophagus. |
