Project Description: The intestine is a vital organ that absorbs nutrients and forms a physical barrier against the outside environment. The lining of the intestine is continuously self-renewed throughout life by stem cells located in the crypt, a pocket-like intestinal gland. At birth, newborns face dramatic environmental changes, among them the introduction of gut microbiota. Although proper intestinal development requires gut microbiota, its influence on intestinal stem cell maturation is unclear. Compromised intestinal development in newborns exposed at birth to the external environment leads to serious diseases, such as necrotizing enterocolitis (NEC), one of the most deadly gastrointestinal diseases in human infants. Currently, how NEC initiates is unknown. This project will investigate whether developmental defects in intestinal stem cells and their altered interaction with gut microbiota underlie the immature intestine and are responsible for NEC initiation. Using mice as a model system, the team will investigate signaling and transcriptional mechanisms of intestinal stem cell differentiation, as well as the role of gut microbiota during development.
Projected Outcomes: This work will define the significance of intestinal stem cells and their differentiated cell populations in development and necrotizing enterocolitis (NEC), as well as identify new biomarkers for infant gut diseases. It will facilitate the development of intestinal stem cell based therapy for NEC.