Submitted on January 6, 2009
Revised on February 9, 2009
Accepted on February 18, 2009
Distinct SOX9 Levels Differentially Mark Stem/Progenitor Populations and Enteroendocrine Cells of the Small Intestine Epithelium
Eric J. Formeister1, Ayn L. Sionas1, David K. Lorance1, Carey L. Barkley1, Ginny H. Lee1, and Scott T. Magness1*
1 University of North Carolina - Chapel Hill
* To whom correspondence should be addressed. E-mail: magness{at}med.unc.edu.
SOX transcription factors have the capacity to modulate stem/progenitor cell proliferation and differentiation in a dose-dependent manner. SOX9 is expressed in the small intestine epithelial stem cell zone, therefore, we hypothesized differential levels of SOX9 may exist, influencing proliferation and/or differentiation of the small intestine epithelium. Sox9 expression levels in the small intestine were investigated using a Sox9EGFP transgenic mouse. Sox9EGFP levels correlate with endogenous SOX9 levels, which are expressed at two steady-state levels, termed Sox9EGFPLO and Sox9EGFPHI. Crypt-based columnar cells are Sox9EGFPLO and demonstrate enriched expression of the stem cell marker, Lgr5. Sox9EGFPHI-cells express Chromogranin-A and Substance-P, but do not express Ki67 and Neurogenin3 indicating Sox9EGFPHI-cells are post-mitotic enteroendocrine cells. Over-expression of SOX9 in a crypt cell line stopped proliferation and induced morphologic changes. These data support a bi-modal role for SOX9 in the intestinal epithelium where low SOX9-expression supports proliferative capacity, while high SOX9-expression suppresses proliferation.
