Nanog-induced intestinal and colonic hyperplasia

Though expression of the homeobox transcription factor Nanog is generally restricted to pluripotent cells and early germ cells, recent reports have found that Nanog is re-expressed in somatic and germ cell tumors associated with poor differentiation and aggressive disease progression. To elucidate its oncogenic properties, a modified Tet-On system was utilised to generate Nanog-inducible mice. By dexamethasone and doxycycline injection, similar Nanog expression levels as in wild-type embryonic stem cells were obtained in all major organs except for brain. Ectopic Nanog expression resulted in intestinal and colonic epithelium hyperplasia-intestinal villi had doubled in length and hyperplastic epithelium outgrowths were seen after 7 days. The tumor suppressor gene Cdx2 was downregulated at onset of Nanog expression, suggesting that crosstalk between Nanog and Cdx2 is conserved from early embryo development to adulthood. Although the mice died before they could form tumors, Cdx2 repression and intestinal hyperplasia links Nanog to tumor initiation. 8 samples were analyzed. Intestine-: Mouse intestine cells without Nanog overexpression, 2 biological rep Intestine+: Mouse intestine cells with Nanog overexpression, 2 biological rep Colon-: Mouse colon cells without Nanog overexpression, 2 biological rep Colon+: Mouse colon cells with Nanog overexpression, 2 biological rep