| First Author | Chen YJ | Year | 2014 |
| Journal | Cell Rep | Volume | 6 |
| Issue | 6 | Pages | 1046-1058 |
| PubMed ID | 24613355 | Mgi Jnum | J:211832 |
| Mgi Id | MGI:5576451 | Doi | 10.1016/j.celrep.2014.02.013 |
| Citation | Chen YJ, et al. (2014) De novo formation of insulin-producing "neo-beta cell islets" from intestinal crypts. Cell Rep 6(6):1046-58 |
| abstractText | The ability to interconvert terminally differentiated cells could serve as a powerful tool for cell-based treatment of degenerative diseases, including diabetes mellitus. To determine which, if any, adult tissues are competent to activate an islet beta cell program, we performed an in vivo screen by expressing three beta cell "reprogramming factors" in a wide spectrum of tissues. We report that transient intestinal expression of these factors-Pdx1, MafA, and Ngn3 (PMN)-promotes rapid conversion of intestinal crypt cells into endocrine cells, which coalesce into "neoislets" below the crypt base. Neoislet cells express insulin and show ultrastructural features of beta cells. Importantly, intestinal neoislets are glucose-responsive and able to ameliorate hyperglycemia in diabetic mice. Moreover, PMN expression in human intestinal "organoids" stimulates the conversion of intestinal epithelial cells into beta-like cells. Our results thus demonstrate that the intestine is an accessible and abundant source of functional insulin-producing cells. |
