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

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  • Formeister, Eric J.
    • Affiliation: School of Medicine, Department of Medicine
  • Magness, Scott T.
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 (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.
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  • Article
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  • In Copyright
Journal title
  • Gastrointestinal and Liver Physiology
Journal volume
  • 296
Journal issue
  • 5
Language
  • English
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  • Postprint
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