Title | In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Li W, Nakanishi M, Zumsteg A, Shear M, Wright C, Melton DA, Zhou Q |
Journal | Elife |
Volume | 3 |
Pagination | e01846 |
Date Published | 2014 Jan 01 |
ISSN | 2050-084X |
Keywords | Animals, 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 |
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(+) 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.01846.001. |
DOI | 10.7554/eLife.01846 |
Alternate Journal | Elife |
PubMed ID | 24714494 |
PubMed Central ID | PMC3977343 |
Grant List | 4 R00 DK077445 / DK / NIDDK NIH HHS / United States |