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Lookup NU author(s): Dr Emma Fairhall, Dr Michelle Charles, Karen Wallace, Claire Schwab, Professor Christine Harrison FRCPath FMedSci, Professor Matthew Wright
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
The rat pancreatic “B-13” acinar cell is a stable progenitor cell line that differentiates into hepatocyte-like cells (B-13/H cells) in 2D un-coated plastic culture with simple culture media in response to glucocorticoid exposure. Examination of cytochrome P450 indicated that the expression of a range of genes were similar to freshly isolated hepatocytes and that these gene products were functional on the basis of spectrophotometrically-detectable reduced carbon-monoxide haemoprotein and metabolism of several drugs. Since normal hepatocytes readily de-differentiate under similar conditions, we hypothesized that B-13 cells have undergone a variety of alterations that stabilise a progenitor phenotype and restrict differentiation to hepatocytes only (which if capitulated in human cells, could generate a readily accessible supply of functional human hepatocytes in vitro). To examine this hypothesis, the B-13 karyotype; pluripotency-inducing transcription factor expression and forced over-expression of these factors in B-13 cells were examined. B-13 cells were also injected into NOD/SCID mice and engraftment and differentiation assessed by RT-PCR, Western blotting, immunohistochemistry and fluorescent in situ hybridization (FISH). B-13 cells expressed four pluripotency-inducing transcription factors c-Myc, Klf4, Oct4 and Sox2 with only c-Myc expression maintained after glucocorticoid treatment. Over-expression of the pluripotency-inducing transcription factors blocked B-13/H formation in response to glucocorticoid. Injection of B-13 cells into NOD/SCID mice resulted in their engraftment to the pancreas and liver, with restricted differentiation to hepatocytes in the liver. The cells did not engraft to any other tissues examined. The ability of B-13 cells to specifically generate functional hepatocytes in vitro in response to glucocorticoid is therefore associated with genetic rearrangements that may facilitate expression of genes associated with plasticity (without leading to pluripotency), which are repressed by glucocorticoid treatment
Author(s): Fairhall EA, Charles MA, Wallace K, Schwab CJ, Harrison CJ, Richter M, Hoffmann SA, Charlton KA, Zeilinger K, Wright MC
Publication type: Article
Publication status: Published
Journal: Toxicology Research
Year: 2013
Volume: 2
Issue: 5
Pages: 308-320
Print publication date: 01/09/2013
Online publication date: 24/06/2013
Acceptance date: 21/06/2013
Date deposited: 05/11/2015
ISSN (print): 2045-452X
ISSN (electronic): 2045-4538
Publisher: RSC Publications
URL: http://dx.doi.org/10.1039/c3tx50030f
DOI: 10.1039/c3tx50030f
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