5-azacytidine promotes terminal differentiation of hepatic progenitor cells

He,Yun; Cui,Jiejie; He,Tongchuan; Bi,Yang

doi:10.3892/mmr.2015.3772

5-azacytidine promotes terminal differentiation of hepatic progenitor cells

Authors:
- Yun He
- Jiejie Cui
- Tongchuan He
- Yang Bi
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Affiliations: Department of Pediatric Surgery, The Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China, Stem Cell Biology and Therapy Laboratory, The Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China
Published online on: May 12, 2015 https://doi.org/10.3892/mmr.2015.3772
Pages: 2872-2878

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Abstract

5-azacytidine (5-azaC) is known to induce cardiomyocyte differentiation. However, its function in hepatocyte differentiation is unclear. The present study investigated the in vitro capability of 5‑azaC to promote maturation and differentiation of mouse embryonic hepatic progenitor cells, with the aim of developing an approach for improving hepatic differentiation. Mouse embryonic hepatic progenitor cells (HP14.5 cells) were treated with 5‑azaC at concentrations from 0 to 20 µmol/l, in addition to hepatocyte induction culture medium. Hepatocyte induction medium induces HP14.5 cell differentiation. 5‑azaC may enhance the albumin promotor‑driven Gaussia luciferase (ALB‑GLuc) activity in induced HP14.5 cells. In the present study 2 µmol/l was found to be the optimum concentration with which to achieve this. The expression of hepatocyte‑associated factors was not significantly different between the group treated with 5‑azaC alone and the control group. The mRNA levels of ALB; cytokeratin 18 (CK18); tyrosine aminotransferase (TAT); and cytochrome p450, family 1, member A1 (CYP1A1); in addition to the protein levels of ALB, CK18 and uridine diphosphate glucuronyltransferase 1A (UGT1A) in the induced group with 5‑azaC, were higher than those in the induced group without 5‑azaC, although no significant differences were detected in expression of the hepatic stem cell markers, DLK and α‑fetoprotein, between the two groups. Treatment with 5‑azaC alone did not affect glycogen synthesis or indocyanine green (ICG) metabolic function in HP14.5 cells, although it significantly increased ICG uptake and periodic acid‑Schiff‑positive cell numbers amongst HP14.5 cells. Therefore, the present study demonstrated that treatment with 5‑azaC alone exerted no effects on the maturation and differentiation of HP14.5 cells. However, 5‑azaC exhibited a synergistic effect on the terminal differentiation of induced hepatic progenitor cells in association with a hepatic induction medium.

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