Hnf4 α is a key gene that can generate columnar metaplasia in oesophageal epithelium.

Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium. Differentiation. 2016 Nov 19;93:39-49 Authors: Colleypriest BJ, Burke ZD, Griffiths LP, Chen Y, Yu WY, Jover R, Bock M, Biddlestone L, Quinlan JM, Ward SG, Mark Farrant J, Slack JM, Tosh D Abstract Barrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4α were ectopically expressed by adenoviral infection. The phenotype following infection was determined by a combination of PCR, immunohistochemical and morphological analyses. We demonstrate the expression of CDX2 and HNF4α in human biopsy samples. Our oesophageal organ culture system expressed markers characteristic of the normal SSQE: p63, K14, K4 and loricrin. Ectopic expression of HNF4α, but not of Cdx2 induced expression of Tff3, villin, K8 and E-cadherin. HNF4α is sufficient to induce a columnar-like phenotype i...
Source: Differentiation - Category: Research Authors: Tags: Differentiation Source Type: research