Pdx1 maintains β cell identity and function by repressing an α cell program

Cell Metab. 2014 Feb 4;19(2):259-71. doi: 10.1016/j.cmet.2013.12.002.


Pdx1 is a homeobox-containing transcription factor that plays a key role in pancreatic development and adult β cell function. In this study, we traced the fate of adult β cells after Pdx1 deletion. As expected, β-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 α cells, indicating that a robust cellular reprogramming had occurred. Reprogrammed cells exhibited a global transcriptional shift that included derepression of the α cell transcription factor MafB, resulting in a transcriptional profile that closely resembled that of α cells. These findings indicate that Pdx1 acts as a master regulator of β cell fate by simultaneously activating genes essential for β cell identity and repressing those associated with α cell identity. We discuss the significance of these findings in the context of the emerging notion that loss of β cell identity contributes to the pathogenesis of type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Chromatin Immunoprecipitation
  • Glucagon-Secreting Cells / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Insulin-Secreting Cells / metabolism*
  • MafB Transcription Factor / genetics
  • MafB Transcription Factor / metabolism
  • Mice
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*


  • Homeodomain Proteins
  • MafB Transcription Factor
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein