期刊
CELL METABOLISM
卷 19, 期 2, 页码 259-271出版社
CELL PRESS
DOI: 10.1016/j.cmet.2013.12.002
关键词
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资金
- NIH/NIDDK [DK083355, DK083111, DK050203, DK089529, 5T32 DK07563]
- Penn Center for Molecular Studies in Digestive and Liver Diseases [P30-DK050306]
- Penn Institute for Diabetes Obesity and Metabolism
- Penn Diabetes Research Center [DK19525]
- Pew Charitable Trusts
- Abramson Family Cancer Research Institute
Pdx1 is a homeobox-containing transcription factor that plays a key role in pancreatic development and adult beta cell function. In this study, we traced the fate of adult beta cells after Pdx1 deletion. As expected, beta-cell-specific removal of Pdx1 resulted in severe hyperglycemia within days. Surprisingly, a large fraction of Pdx1-deleted cells rapidly acquired ultrastructural and physiological features of a cells, indicating that a robust cellular reprogramming had occurred. Reprogrammed cells exhibited a global transcriptional shift that included derepression of the alpha cell transcription factor MafB, resulting in a transcriptional profile that closely resembled that of alpha cells. These findings indicate that Pdx1 acts as a master regulator of beta cell fate by simultaneously activating genes essential for beta cell identity and repressing those associated with alpha cell identity. We discuss the significance of these findings in the context of the emerging notion that loss of beta cell identity contributes to the pathogenesis of type 2 diabetes.
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