In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes.

ABSTRACT: Direct 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(+) ?-cells, glucagon(+) ?-cells, and somatostatin(+) ?-cells. We previously reported that a combination of three transcription factors, Ngn3, Mafa, and Pdx1, directly reprograms pancreatic acinar cells to ?-cells. We now show that acinar cells can be converted to ?-like and ?-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 ?-specification in the absence of other factors. ?-specification is in turn suppressed by Mafa and Pdx1 during ?- and ?-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.01846.001.

SUBMITTER: Li W 

PROVIDER: S-EPMC3977343 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature