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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/G418    most recent 00418.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Lussier, C. R. Articles by Boudreau, F. Search for Related Content PubMed PubMed Citation Articles by Lussier, C. R. Articles by Boudreau, F.

MUCOSAL BIOLOGY

Hepatocyte nuclear factor-4 promotes differentiation of intestinal epithelial cells in a coculture system

Canadian Institute of Health Research Team on Digestive Epithelium, Département d'Anatomie et Biologie Cellulaire, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Québec, Canada

Submitted 15 September 2007 ; accepted in final form 17 November 2007

Normal cellular models able to efficiently recapitulate intestinal epithelial cell differentiation in culture are not yet available. The aim of this work was to establish and genetically characterize a mesenchymal-epithelial coculture system to identify transcriptional regulators involved in this process. The deposition of rat intestinal epithelial cells on human intestinal mesenchymal cells led to the formation of clustered structures that expanded shortly after seeding. These structures were composed of polarized epithelial cells with brush borders and cell junction complexes. A rat GeneChip statistical analysis performed at different time points during this process identified hepatocyte nuclear factor-4 (HNF-4) and hepatocyte nuclear factor-1 (HNF-1) as being induced coincidently with the apparition of polarized epithelial structures. Stable introduction of HNF-4 in undifferentiated epithelial cells alone led to the rapid induction of HNF-1 and several intestinal-specific markers and metabolism-related genes for which mRNA was identified to be upregulated during epithelial differentiation. HNF-4 was capable to transactivate the calbindin 3 gene promoter, a process that was synergistically increased in the presence of HNF-1. When HNF-4-expressing cells were plated on mesenchymal cells, an epithelial monolayer formed rapidly with the apparition of dome structures that are characteristics of vectorial ion transport. Forced expression of HNF-1 alone did not result in dome structures formation. In sum, this novel coculture system functionally identified for the first time HNF-4 as an important modulator of intestinal epithelial differentiation and offers an innovative opportunity to investigate molecular mechanisms involved in this process.

intestinal epithelial cells; mesenchymal cells; HNF-4; HNF-1; differentiation

This article has been cited by other articles:

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