SOX9EGFPhi cells are a heterogenous population in the adult intestinal crypt (2013)
Undergraduate: Xiao Fu Liu
Faculty Advisor: Scott Magness
Department: Biology
Recent studies suggest there are two distinct populations of intestinal epithelial stem cells (IESCs), fast cycling ¿active¿ IESCs located at the crypt base that regenerate under homeostatic conditions and ¿reserve¿ IESCs located at the +4 position that are activated upon damage. Our lab and others have shown that high levels of the Sox9 transcription factor (Sox9HI) mark a population of cells that exhibit both enteroendocrine (EE) and ¿reserve¿ stem cell features. We hypothesized that Sox9EGFPHI cells are a heterogeneous population containing differentiated EE cells and reserve IESCs. To characterize Sox9HI cells, we used a Sox9EGFP reporter mouse in which different levels of Sox9 expression mark distinct epithelial populations. Birth-dating studies demonstrated 1.1% of chromogranin A positive EE cells are long-lived and remain in the crypt for at least 6 weeks. Immunohistochemistry performed on adult mouse small intestine showed three distinct populations of Sox9EGFPHI cells: SOX9EGFPHI:ChgA positive EE cells, SOX9EGFPHI:Dcamkl-1 positive cells, and SOX9EGFPHI cells which were negative for both ChgA and Dcamkl-1. Sox9EGFPHI:ChgA- cell populations were found to localize predominately to the +4-5 crypt position, the putative location of reserve IESCs. Analysis by qRT-PCR showed enrichment of putative reserve IESC markers, Bmi1 and HopX, in the Sox9EGFPHI population. These studies suggest that a subset of Sox9EGFPHI cells exhibit stem cell features.