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PMID: 17563382 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Sox9 coordinates a transcriptional network in pancreatic progenitor cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 25 ·2007-06-19 ·Pages 10500-5

Lynn FC, Smith SB, Wilson ME, Yang KY, Nekrep N, German MS

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.

MeSH Terms
Animals Binding Sites Cell Line Gene Regulatory Networks/physiology Genes, Reporter High Mobility Group Proteins/genetics,metabolism Immunohistochemistry Luciferases/metabolism Mice Mice, Inbred Strains Models, Biological Pancreas/cytology RNA Interference SOX9 Transcription Factor Stem Cells/metabolism,physiology Transcription Factors/genetics,metabolism Transcription, Genetic Transfection
Chemicals
High Mobility Group Proteins SOX9 Transcription Factor SOX9 protein, human Sox9 protein, mouse Transcription Factors Luciferases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lynn F C
Diabetes Center, Hormone Research Institute, and Department of Medicine, University of California, San Francisco, CA 94143, USA.
Smith S B
Wilson M E
Yang K Y
Nekrep N
German M S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0704054104
Published
2007-06-19
Epub
2007-00-11
Pages
10500-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1965542
Subset
IM
Grants
NIDDK NIH HHS · P30 DK063720 · United States
NIDDK NIH HHS · R01 DK021344 · United States
NIDDK NIH HHS · R56 DK021344 · United States
NIDDK NIH HHS · U19 DK061245 · United States
NIDDK NIH HHS · DK61245 · United States
NIDDK NIH HHS · DK21344 · United States
External Links
PubMed source DOI: 10.1073/pnas.0704054104 PMC Full Text View journal details
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