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Am J Physiol Gastrointest Liver Physiol 296: G1108-G1118, 2009. First published February 19, 2009; doi:10.1152/ajpgi.00004.2009
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MUCOSAL BIOLOGY

Distinct SOX9 levels differentially mark stem/progenitor populations and enteroendocrine cells of the small intestine epithelium

Eric J. Formeister, Ayn L. Sionas, David K. Lorance, Carey L. Barkley, Ginny H. Lee, and Scott T. Magness

Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill

Submitted 6 January 2009 ; accepted in final form 18 February 2009

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 that 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 Sox9 enhanced green fluorescent protein (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 that Sox9EGFPHI cells are postmitotic enteroendocrine cells. Overexpression of SOX9 in a crypt cell line stopped proliferation and induced morphological changes. These data support a bimodal role for SOX9 in the intestinal epithelium, where low SOX9 expression supports proliferative capacity, and high SOX9 expression suppresses proliferation.

intestinal epithelial development; stem cell; progenitor cell


Address for reprint requests and other correspondence: S. T. Magness, Univ. of North Carolina at Chapel Hill, 101A Mason Farm Rd. CB# 7032, MBRB Rm. 7332, Chapel Hill, NC 27599 (e-mail: magness{at}med.unc.edu)






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