Establishment and transcriptomic features of an immortalized hepatic cell line of the Chinese tree shrew

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GENOMICS, TRANSCRIPTOMICS, PROTEOMICS

Establishment and transcriptomic features of an immortalized hepatic cell line of the Chinese tree shrew Xuemei Zhang 1 & Dandan Yu 2 & Yong Wu 2 & Tianle Gu 2,3 & Na Ma 1 & Shaozhong Dong 1 & Yong-Gang Yao 2,3,4 Received: 19 June 2020 / Revised: 3 August 2020 / Accepted: 23 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

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. Keywords Immortalized hepatic cell line . Tree shrew . RNA-sequencing . Dynamic expression profile

Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00253-020-10855-x) contains supplementary material, which is available to authorized users. * Dandan Yu [email protected]

2

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, and KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China

3

Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, Yunnan, China

4

National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, Yunnan, China

* Shaozhong Dong [email protected] 1

Yunnan Key