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 ( Sox9EGFP) transgenic mouse. Sox9EGFPlevels correlate with endogenous SOX9 levels, which are expressed at two steady-state levels, termed Sox9EGFPLOand Sox9EGFPHI. Crypt-based columnar cells are Sox9EGFPLOand demonstrate enriched expression of the stem cell marker, Lgr5. Sox9EGFPHIcells express chromogranin A and substance P but do not express Ki67 and neurogenin3, indicating that Sox9EGFPHIcells 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.