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

TitleIn vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes.
Publication TypeJournal Article
Year of Publication2014
AuthorsLi W, Nakanishi M, Zumsteg A, Shear M, Wright C, Melton DA, Zhou Q
Date Published2014 Jan 01
KeywordsAnimals, Basic Helix-Loop-Helix Transcription Factors, Cell Lineage, Cell Transdifferentiation, Cellular Reprogramming, Gene Expression Regulation, Developmental, Genes, Reporter, Glucagon-Secreting Cells, HEK293 Cells, Homeodomain Proteins, Humans, Insulin-Secreting Cells, Luminescent Proteins, Maf Transcription Factors, Large, Mice, Knockout, Nerve Tissue Proteins, Pancreas, Exocrine, Somatostatin-Secreting Cells, Time Factors, Trans-Activators, Transfection

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:

Alternate JournalElife
PubMed ID24714494
PubMed Central IDPMC3977343
Grant List4 R00 DK077445 / DK / NIDDK NIH HHS / United States