Combinational Overexpression of Foxa3 and Hnf4a Enhance the Proliferation and Prolong the Functional Maintenance of Primary Hepatocytes

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Abstract

In an in vitro culture system, primary hepatocytes usually display a low proliferation capacity, accompanied with a decrease of viability and a loss of hepatocyte-specific functions. Previous studies have demonstrated that the combination introductions of certain hepatocyte-specific transcription factors are able to convert fibroblasts into functional hepatocyte-like cells. However, such combinational usage of transcription factors in primary hepatocytes culture has not yet sufficiently studied. The forkhead box protein A3 (FoxA3) and hepatocyte nuclear factor 4α (Hnf4α) are liver-enriched transcription factors that play vital roles in the differentiation, and maintenance of hepatocytes. Thus, we simultaneously overexpressed the two genes, Foxa3 and Hnf4a, in rat hepatocytes and observed that the combinational augmentation of these two transcription factors have enhanced the proliferation and stabilized the hepatocyte-specific functions of primary hepatocytes over a long-term culture period.

About the authors

J. Y. Fan

Stem Cell and Biotherapy Engineering Research Center of Henan,
Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University,
East of JinSui Road 601; College of Life Science and Technology, Xinxiang Medical University, Henan; Shandong Tianchuan Precision Medical Technology Co. Ltd.

Email: linjtlin@126.com
China, 453003, Xinxiang; China, 453003, Xinxiang; China, 253084, Dezhou

G. Dama

Stem Cell and Biotherapy Engineering Research Center of Henan,
Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University,
East of JinSui Road 601; Department of Community Health, Advanced Medical and Dental Institute, Universiti Sains Malaysia

Email: linjtlin@126.com
China, 453003, Xinxiang; Malaysia, 13200, Kepala Batas

Y. L. Liu

Stem Cell and Biotherapy Engineering Research Center of Henan,
Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University,
East of JinSui Road 601; College of Life Science and Technology, Xinxiang Medical University, Henan

Email: linjtlin@126.com
China, 453003, Xinxiang; China, 453003, Xinxiang

W. Y. Guo

College of Life Science and Technology, Xinxiang Medical University, Henan

Email: linjtlin@126.com
China, 453003, Xinxiang

J. T. Lin

Stem Cell and Biotherapy Engineering Research Center of Henan,
Henan Joint International Research Laboratory of Stem Cell Medicine, Xinxiang Medical University,
East of JinSui Road 601; College of Life Science and Technology, Xinxiang Medical University, Henan; College of Biomedical Engineering, Xinxiang Medical University, Henan

Author for correspondence.
Email: linjtlin@126.com
China, 453003, Xinxiang; China, 453003, Xinxiang; China, 453003, Xinxiang

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Copyright (c) 2023 J.Y. Fan, G. Dama, Y.L. Liu, W.Y. Guo, J.T. Lin