Li W, Nakanishi M, Zumsteg A, Shear M, Wright C, Melton DA, Zhou Q. 2014. In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes. eLife. 3:e01846. Pubmed: 24714494 DOI:10.7554/eLife.01846


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(+) 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:

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Doug Melton is pursuing a cure for type 1 diabetes. His lab studies the developmental biology of the pancreas, using that information to grow and develop pancreatic cells (islets of Langerhans). In parallel, they investigate ways to protect beta cells from autoimmune attack.

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