Li, WeidaNakanishi, MioZumsteg, AdrianShear, MatthewWright, ChristopherMelton, DouglasZhou, Qiao2014-05-062014Li, Weida, Mio Nakanishi, Adrian Zumsteg, Matthew Shear, Christopher Wright, Douglas A Melton, and Qiao Zhou. 2014. “In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes.” eLife 3 (1): e01846. doi:10.7554/eLife.01846. http://dx.doi.org/10.7554/eLife.01846.2050-084Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12152833Direct lineage conversion of adult cells is a promising approach for regenerative medicine. A major challenge of lineage conversion is to generate specific cell subtypes. The pancreatic islets contain three major hormone-secreting endocrine subtypes: insulin+ β-cells, glucagon+ α-cells, and somatostatin+ δ-cells. We previously reported that a combination of three transcription factors, Ngn3, Mafa, and Pdx1, directly reprograms pancreatic acinar cells to β-cells. We now show that acinar cells can be converted to δ-like and α-like cells by Ngn3 and Ngn3+Mafa respectively. Thus, three major islet endocrine subtypes can be derived by acinar reprogramming. Ngn3 promotes establishment of a generic endocrine state in acinar cells, and also promotes δ-specification in the absence of other factors. δ-specification is in turn suppressed by Mafa and Pdx1 during α- and β-cell induction. These studies identify a set of defined factors whose combinatorial actions reprogram acinar cells to distinct islet endocrine subtypes in vivo. DOI: http://dx.doi.org/10.7554/eLife.01846.001en-USpancreatic endocrine cellsdirect lineage conversionin vivo reprogrammingacinar to endocrine conversionislet delta, alpha, beta cellsmouseJournal Article2014-05-0610.7554/eLife.01846