Extended Data Figure 7. Ectopic CDX2 expression promotes intestinal metaplasia of the transitional epithelium.

a, Intestinal metaplasia occurs in Krt5-rtTA;otet-CDX2 mutants fed with Dox-containing water for 3 months as shown by PAS staining. n=5 per group. b, Goblet cell enriched with vesicles (stars) present in the SCJ of Krt5-rtTA;otet-CDX2 mutants following 3-month Dox treatment as shown by electron microscope. n=3 per group. c, KRT7 is expressed by both BE and MLE but not the neighboring squamous epithelium. Residual CDX2 is expressed in a subpopulation of the metaplastic columnar cells although KRT5 expression is not detectable. n=5 per group. d, Reduced expression of basal cell genes (p63, Krt5) and increased expression of the intestinal genes (Villin1, Agr2, Muc2, Muc4, TFF3) during intestinalization of the SCJ following CDX2 overexpression. (ns, p>0.05; *p<0.05; **p<0.001; two-tailed Student’s t-test; n=3 independent experiments) e, Normal SCJ structure is maintained in control mice (otet-CDX2-T2A-mCherry) following 3-month Dox treatment. n=5. f, CDX2 overexpression does not promote columnar metaplasia in the oesophagus and forestomach. Squamous hyperplasia is present in the forestomach (dotted black line). Note that CDX2 expression does not induce ectopic expression of KRT7 in the stratified squamous epithelium. n=5. Abbreviation: Sq, stratified squamous epithelium; Co, columnar epithelium; G, goblet; N, nucleus. Scale bar, 20 μm.