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

Am J Physiol Gastrointest Liver Physiol. 2009 May;296(5):G1108-18. doi: 10.1152/ajpgi.00004.2009. Epub 2009 Feb 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation* / genetics
  • Cell Line
  • Cell Proliferation*
  • Cell Shape
  • Chromogranin A / metabolism
  • Enteroendocrine Cells / metabolism*
  • Gene Expression Regulation
  • Genes, Reporter
  • Genotype
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism*
  • Intestine, Small / cytology
  • Intestine, Small / metabolism*
  • Mice
  • Mice, Transgenic
  • Paneth Cells / metabolism
  • Phenotype
  • Rats
  • Receptors, G-Protein-Coupled / metabolism
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism*
  • Stem Cells / metabolism*
  • Substance P / metabolism
  • Transduction, Genetic


  • Chromogranin A
  • Lgr5 protein, mouse
  • Receptors, G-Protein-Coupled
  • SOX9 Transcription Factor
  • Sox9 protein, mouse
  • Substance P