Sox9 coordinates a transcriptional network in pancreatic progenitor cells

Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10500-5. doi: 10.1073/pnas.0704054104. Epub 2007 Jun 11.

Abstract

During pancreas development, both the exocrine and endocrine lineages differentiate from a common pool of progenitor cells with similarities to mature pancreatic duct cells. A small set of transcription factors, including Tcf2, Onecut1, and Foxa2, has been identified in these pancreatic progenitor cells. The Sry/HMG box transcription factor Sox9 is also expressed in the early pancreatic epithelium and is required for normal pancreatic exocrine and endocrine development in humans. In this study, we found Sox9 in mice specifically expressed with the other progenitor transcription factors in both pancreatic progenitor cells and duct cells in the adult pancreas. Sox9 directly bound to all three genes in vitro and in intact cells, and regulated their expression. In turn, both Foxa2 and Tcf2 regulated Sox9 expression, demonstrating feedback circuits between these genes. Furthermore, Sox9 activated the expression of the proendocrine factor Neurogenin3, which also depends on the other members of the progenitor transcription network. These studies indicate that Sox9 plays a dual role in pancreatic progenitor cells: both maintaining a stable transcriptional network and supporting the programs by which these cells differentiate into distinct lineages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • Gene Regulatory Networks / physiology*
  • Genes, Reporter
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Immunohistochemistry
  • Luciferases / metabolism
  • Mice
  • Mice, Inbred Strains
  • Models, Biological
  • Pancreas / cytology*
  • RNA Interference
  • SOX9 Transcription Factor
  • Stem Cells / metabolism
  • Stem Cells / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transfection

Substances

  • High Mobility Group Proteins
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Sox9 protein, mouse
  • Transcription Factors
  • Luciferases