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HNF4alpha expression amplifies the glucocorticoid-induced conversion of a human pancreatic cell line to an hepatocyte-like cell

Lookup NU author(s): Dr Emma Fairhall, Dr Alistair Leitch, Anne Lakey, Dr Tarek Mamdouh AbdelghanyORCiD, Dr Ibrahim Ibrahim, Colin Wilson, Professor Matthew Wright



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


The pancreas and liver are closely related developmentally and trans-differentiation of cells from one tissue into the cells of the other has been documented to occur after injury or exposure to selected growth factors or glucocorticoid hormones. To generate a readily-expandable source of human hepatocyte-like (H-13) cells, the human pancreatic adenocarcinoma cell (HPAC) line was stably transfected with a construct encoding the variant 2 hepatocyte nuclear factor 4 α (HNF4α) using a piggyBac vector and transient expression of a transposase. Through induction of transgene HNF4α regulated via an upstream glucocorticoid response element in combination with existing modulating effects of glucocorticoid, H-13 cells were converted into quantitatively similar hepatocyte-like (H-13/H) cells based on expression of a variety of hepatocyte proteins. H-13/H cells also demonstrated the ability to store glycogen and lipids. These data provide proof of concept that regulated expression of genes associated with hepatocyte phenotype could be used to generate quantitatively functional human hepatocyte-like cells using a readily expandable cell source and simple culture protocol. This approach would have utility in Toxicology and Hepatology research.

Publication metadata

Author(s): Fairhall EA, Leitch AC, Lakey AF, Abdelghany TM, Ibrahim I, Tosh D, Kass GE, Wilson C, Wright MC

Publication type: Article

Publication status: Published

Journal: Biochemical and Biophysical Research Communications

Year: 2018

Volume: 503

Issue: 3

Pages: 1633-1640

Print publication date: 10/09/2018

Online publication date: 26/07/2018

Acceptance date: 20/07/2018

Date deposited: 20/07/2018

ISSN (print): 0006-291X

ISSN (electronic): 1090-2104

Publisher: Elsevier Inc.


DOI: 10.1016/j.bbrc.2018.07.092


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Funder referenceFunder name
Europea n Union's Seventh Framework Prog ramme
National Institute for Health Research