Loss of GATA4 causes ectopic pancreas in the stomach

Pancreatic heterotopia is defined as pancreatic tissue outside its normal location in the body and anatomically separated from the pancreas. In this work we have analyzed the stomach glandular epithelium of Gata4 flox/flox; Pdx1‐Cre mice (Gata4KO mice). We found that Gata4KO glandular epithelium displays an atypical morphology similar to the cornified squamous epithelium and exhibits upregulation of forestomach markers. The developing gastric units fail to form properly, and the glandular epithelial cells do not express markers of gastric gland in the absence of GATA4. Of interest, the developing glands of the Gata4KO stomach express pancreatic cell markers. Furthermore, a mass of pancreatic tissue located in the subserosa of the Gata4KO stomach is observed at adult stages. Heterotopic pancreas found in Gata4‐deficient mice contains all three pancreatic cell lineages: ductal, acinar, and endocrine. Moreover, Gata4 expression is downregulated in ectopic pancreatic tissue of some human biopsy samples.
ER‐S. was supported by a ‘Juan de la Cierva’ postdoctoral fellowship from the Spanish Ministry of Economy and Competitiveness (IJCI‐2014‐19251). LV was supported by a contract from Spanish Ministry of Economy and Competitiveness (RYC‐2013‐14533). This work was supported by grants from the Spanish Ministry of Economy and Competitiveness BFU2017‐82497‐P to AR, ISCIII‐Subdirección General de Evaluación y Fomento de la Investigación co‐funded with Fondos FEDER, PI16/00175 to DAC, the Andalusian Ministry of Science and Innovation CTS‐7478 to DAC, and grant SAF2015‐70553‐R to FXR. CNIO is supported by the “Ministerio de Ciencia, Innovación y Universidades” as a Centro de Excelencia Severo Ochoa (SEV‐2015‐0510).