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CFTR constrains the differentiation from mouse embryonic stem cells to intestine lineage cells



CFTR constrains the differentiation from mouse embryonic stem cells to intestine lineage cells



Biochemical and Biophysical Research Communications 2019



Cystic fibrosis transmembrane conductance regulator (CFTR) is a transmembrane Cl- and HCO3- transporter and its malfunction leads to cystic fibrosis (CF) and multiple congenital diseases. The most common mutation in CF patient is DF508 and the patients have increased risk in developing gastrointestinal tumors. To explore the etiology of high cancer risk in DF508-CF patients, we have derived mouse DF508-CFTR embryonic stem (ES) cells and use it as a novel in vitro model to study the role of CFTR from developmental angle. We found the self-renewal properties are intact in DF508-CFTR ES cells. Nevertheless, the differentiation of intestine lineage, the expression of intestine progenitor and major intestine differentiated cell markers is significantly upregulated in DF508-CFTR ES cell differentiated cells. Therefore, CFTR plays an important role in intestine lineage differentiation. Besides, DF508-CFTR ES cells formed teratomas demonstrated enhanced expressions of cell proliferation, migration and epithelial-mesenchymal transition associated marker genes, indicating the tumor suppressive role of CFTR. Taken together, our derived DF508-CFTR ES cells can serve as a new model to study the etiology of CF disease in vitro and malignant teratoma formation in vivo.

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Accession: 066446816

Download citation: RISBibTeXText

PMID: 30704755

DOI: 10.1016/j.bbrc.2019.01.100


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