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Elife. 2014 Jan 1;3:e01846. doi: 10.7554/eLife.01846.

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

Author information

1
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States.

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.

KEYWORDS:

acinar to endocrine conversion; direct lineage conversion; in vivo reprogramming; islet delta, alpha, beta cells; pancreatic endocrine cells

PMID:
24714494
PMCID:
PMC3977343
DOI:
10.7554/eLife.01846
[Indexed for MEDLINE]
Free PMC Article

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