Reprogramming of adult gut stem cells into insulin-secreting cells
Developmental biology informs us that the pancreas and the intestine are closely related tissues. While the pancreas gives rise to five different endocrine cell types, the intestine is the site of the largest endocrine organ in the body, producing up to 20 different endocrine cell types. Interestingly, the progenitor cells of the pancreas and the intestine employ common transcriptional machinery to specify their endocrine populations during development. Because the transcriptional profiles are very similar, there must be other mechanisms that maintain separate pancreas and intestinal cellular fates. We are interested in the role of DNA methylation in defining and maintaining the cellular identities of closely related cell types. We are interested in exploiting these small differences to mediate cellular reprogramming of intestinal stem cells to insulin-secreting pancreatic beta-like cells.