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SPDEF, also called PDEF (prostate derived ETS factor) or PSE (prostate specific ETS) is an ETS domain transcription factor which is highly expressed in intestinal goblet cells.
Using a transgenic drug-inducible system, we recently discovered that SPDEF can control both intestinal progenitor proliferation as well as cell fate. When SPDEF is expressed throughout the progenitors of the crypt, proliferation is dramatically reduced, and progenitor cells adopt a goblet cell fate.
Thus, in addition to increased goblet cells, we observed a significant reduction in Paneth, enteroendocrine, and absorptive enterocytes in SPDEF-expressing intestines.
Current projects in the lab seek to elucidate the mechanisms by which SPDEF controls intestinal cell fate, and whether this terminal differentiation factor plays a role in colorectal cancer.
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SPDEF (antibody staining in brown) is highly expressed in developing goblet cells (stained for mucus with alcian blue) within the small intestinal crypts, and continues to be expressed by mature goblet cells on the villi. Weaker SPDEF staining is detected in some Paneth cells at the crypt base.
Transgenic mice that express SPDEF under the control of a tetracycline-inducible promoter were treated with tetracycline for 28 days. Immunofluorescent staining of the ileum for the goblet cell mucin Muc2 (green) showed a dramatic increase in the number of goblet cells in the epithelium of transgenic mice (Right) compared to wild type littermate controls (Left).
Transgenic mice that express SPDEF under the control of a tetracycline-inducible promoter were treated with tetracycline for 28 days. At the top, plastic embedded sections of crypts were stained with periodic acid/Schiff’s reagent (pink) for sugars in goblet and Paneth cells, and for the Paneth cell marker lysozyme (brown). Below, serial sections of the crypts shown at top were imaged by electron microscopy. Paneth cells were absent from SPDEF expressing transgenic mice, and were replaced by goblet cells.
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