1. Distinct SOX9 levels differentially mark stem/progenitor populations and enteroendocrine cells of the small intestine epithelium.
- Author
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Formeister EJ, Sionas AL, Lorance DK, Barkley CL, Lee GH, and Magness ST
- Subjects
- Animals, Cell Line, Cell Shape, Chromogranin A metabolism, Gene Expression Regulation, Genes, Reporter, Genotype, Intestinal Mucosa cytology, Intestine, Small cytology, Mice, Mice, Transgenic, Paneth Cells metabolism, Phenotype, Rats, Receptors, G-Protein-Coupled metabolism, SOX9 Transcription Factor genetics, Substance P metabolism, Transduction, Genetic, Cell Differentiation genetics, Cell Proliferation, Enteroendocrine Cells metabolism, Intestinal Mucosa metabolism, Intestine, Small metabolism, SOX9 Transcription Factor metabolism, Stem Cells metabolism
- Abstract
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 (Sox9(EGFP)) transgenic mouse. Sox9(EGFP) levels correlate with endogenous SOX9 levels, which are expressed at two steady-state levels, termed Sox9(EGFPLO) and Sox9(EGFPHI). Crypt-based columnar cells are Sox9(EGFPLO) and demonstrate enriched expression of the stem cell marker, Lgr5. Sox9(EGFPHI) cells express chromogranin A and substance P but do not express Ki67 and neurogenin3, indicating that Sox9(EGFPHI) 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.
- Published
- 2009
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