PMID- 19228882 OWN - NLM STAT- MEDLINE DCOM- 20090602 LR - 20220317 IS - 0193-1857 (Print) IS - 1522-1547 (Electronic) IS - 0193-1857 (Linking) VI - 296 IP - 5 DP - 2009 May TI - Distinct SOX9 levels differentially mark stem/progenitor populations and enteroendocrine cells of the small intestine epithelium. PG - G1108-18 LID - 10.1152/ajpgi.00004.2009 [doi] AB - 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. FAU - Formeister, Eric J AU - Formeister EJ AD - Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, NC 27599, USA. FAU - Sionas, Ayn L AU - Sionas AL FAU - Lorance, David K AU - Lorance DK FAU - Barkley, Carey L AU - Barkley CL FAU - Lee, Ginny H AU - Lee GH FAU - Magness, Scott T AU - Magness ST LA - eng GR - P30 DK034987/DK/NIDDK NIH HHS/United States GR - P30 NS045892/NS/NINDS NIH HHS/United States GR - 5P30DK034987/DK/NIDDK NIH HHS/United States GR - 1-K01-DK080181-01/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090219 PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 RN - 0 (Chromogranin A) RN - 0 (Lgr5 protein, mouse) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (SOX9 Transcription Factor) RN - 0 (Sox9 protein, mouse) RN - 33507-63-0 (Substance P) SB - IM MH - Animals MH - *Cell Differentiation/genetics MH - Cell Line MH - *Cell Proliferation MH - Cell Shape MH - Chromogranin A/metabolism MH - Enteroendocrine Cells/*metabolism MH - Gene Expression Regulation MH - Genes, Reporter MH - Genotype MH - Intestinal Mucosa/cytology/*metabolism MH - Intestine, Small/cytology/*metabolism MH - Mice MH - Mice, Transgenic MH - Paneth Cells/metabolism MH - Phenotype MH - Rats MH - Receptors, G-Protein-Coupled/metabolism MH - SOX9 Transcription Factor/genetics/*metabolism MH - Stem Cells/*metabolism MH - Substance P/metabolism MH - Transduction, Genetic PMC - PMC2696217 EDAT- 2009/02/21 09:00 MHDA- 2009/06/03 09:00 PMCR- 2010/05/01 CRDT- 2009/02/21 09:00 PHST- 2009/02/21 09:00 [entrez] PHST- 2009/02/21 09:00 [pubmed] PHST- 2009/06/03 09:00 [medline] PHST- 2010/05/01 00:00 [pmc-release] AID - 00004.2009 [pii] AID - GI-00004-2009 [pii] AID - 10.1152/ajpgi.00004.2009 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2009 May;296(5):G1108-18. doi: 10.1152/ajpgi.00004.2009. Epub 2009 Feb 19.