title: Distinct SOX9 levels differentially mark stem/progenitor populations and enteroendocrine cells of the small intestine epithelium.
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.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, NC 27599, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Formeister
authors.forename: Ayn L
authors.initials: AL
authors.lastname: Sionas
authors.forename: David K
authors.initials: DK
authors.lastname: Lorance
authors.forename: Carey L
authors.initials: CL
authors.lastname: Barkley
authors.forename: Ginny H
authors.initials: GH
authors.lastname: Lee
authors.forename: Scott T
authors.initials: ST
authors.lastname: Magness
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D048430:Cell Shape; D053379:Chromogranin A / Q000378:metabolism; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005838:Genotype; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D019879:Paneth Cells / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D053379:Chromogranin A; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D013373:Substance P