The Role of Sox9 in the Adult Intestinal Epithelium (2011)
Undergraduate: Kyle Roche
Faculty Advisor: Scott Magness
Department: Biology
The intestinal epithelium regenerates more rapidly than any other tissue. This rapid replacement of intestinal epithelium is driven by a pool of multipotent stem cells that reside in the base of the crypts and is required for normal gut homeostasis and repair following disease or injury. Recent advances in the intestinal epithelial stem cell (IESC) field have transformed the possibility of utilizing these cells for therapeutics by modulating self-renewal, proliferation and differentiation potential – otherwise known as stemness. Sox transcription factors have been shown to have powerful influence in maintaining stemness in various tissue types and they likely play a role in IESCs. We have shown that Sox9 is expressed in IESCs, transit-amplifying progenitors, post-mitotic enteroendocrine cells and Paneth cells. Whether Sox9 is playing an intrinsic and/or extrinsic role in IESC behavior is unknown. We hypothesize that Sox9 plays a role in the maintenance and differentiation of IESCs in the adult intestinal epithelium. Inducible/conditional ablation of Sox9 in the mouse demonstrates that the loss of Sox9 results in increased proliferation within the stem/progenitor cell populations, secretory lineage defects, and aberrant epithelial morphology. Gene expression analysis indicates that the loss of Sox9- affects genes involved in the control of proliferation, migration, cell adhesion and differentiation. These studies demonstrate that Sox9 has a critical role in modulating IESC stemness.