Abstract
Background
The Chinese tree shrew (Tupaia belangeri chinesis) is a rising experimental animal and has been used for studying a variety of human diseases, such as metabolic and viral infectious diseases.
Methods
In this study, we established an immortalized tree shrew hepatic cell line, ITH6.1, by introducing the simian virus 40 large T antigen gene into primary tree shrew hepatocytes (PTHs).
Results
The ITH6.1 cell line had a stable cell morphology and proliferation activity. This cell line could be infected by enterovirus 71 (EV71), but not hepatitis C virus (HCV), although the known HCV entry factors, including CD81, SR-BI, CLDN1 and OCLN, were all expressed in the PTHs and ITH6.1 of different passages. Comparison of the transcriptomic features of the PTHs and different passages of the ITH6.1 cells revealed the dynamic gene expression profiles during the transformation. We found that the DNA replication- and cell cycle-related genes were upregulated, whereas the metabolic pathway-related genes were downregulated in early passages of immortalized hepatocytes compared to the PTHs. Furthermore, expression of hepatocytes function-related genes were repressed in ITH6.1 compared to that of PTHs.
Conclusion
We believe these cellular expression alterations might cause the resistance of the ITH6.1 cell to HCV infection. This tree shrew liver cell line may be a good resource for the field.
Key points
• A tree shrew hepatic cell line (ITH6.1) was established.
• ITH6.1 cells could be infected by EV71, but not HCV.
• ITH6.1 had an altered expression profiling compared to the primary hepatocytes.
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Acknowledgements
We thank the two anonymous reviewers for their helpful comments on the early version of this paper.
Funding
This study was supported by Yunnan Province (2018ZF006 and 2018FB046), the Chinese Academy of Sciences (CAS “Light of West China” Program xbzg-zdsys-201909), and National Natural Science Foundation of China (81571998 and U1902215).
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YGY, SD, and DY conceived and designed the research. NM, DY, XZ, and TG conducted the experiments. YW, NM, and TG analyzed the data. XZ, DY, TG, and YGY wrote the manuscript. All authors read and approved the manuscript.
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All experiments were approved and performed according to the guidelines approved by the Animal Care and Welfare Committee of the Institute of Medical Biology, Chinese Academy of Medical Sciences.
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Zhang, X., Yu, D., Wu, Y. et al. Establishment and transcriptomic features of an immortalized hepatic cell line of the Chinese tree shrew. Appl Microbiol Biotechnol 104, 8813–8823 (2020). https://doi.org/10.1007/s00253-020-10855-x
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DOI: https://doi.org/10.1007/s00253-020-10855-x