In Vitro Three‐Dimensional Liver Models for Nanomaterial DNA Damage Assessment

Scientists consider the benefits, limitations, and adaptations of specific in vitro approaches to assess DNA damage in the liver, whilst identifying critical advancements required to support a multitude of biochemical endpoints.
[Small]
Llewellyn, S. V., Niemeijer, M., Nymark, P., Moné, M. J., Water, B. van de, Conway, G. E., Jenkins, G. J. S., & Doak, S. H. (n.d.). In Vitro Three-Dimensional Liver Models for Nanomaterial DNA Damage Assessment. Small, n/a(n/a), 2006055. https://doi.org/https://doi.org/10.1002/smll.202006055 Cite
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Inhibition of Histone Methyltransferase G9a Attenuates Liver Cancer Initiation by Sensitizing DNA-Damaged Hepatocytes to p53-Induced Apoptosis

Using liver-specific G9a-deficient mice, scientists revealed that loss of G9a significantly attenuated liver tumor initiation caused by diethylnitrosamine.
[Cell Death & Disease]
Nakatsuka, T., Tateishi, K., Kato, H., Fujiwara, H., Yamamoto, K., Kudo, Y., Nakagawa, H., Tanaka, Y., Ijichi, H., Ikenoue, T., Ishizawa, T., Hasegawa, K., Tachibana, M., Shinkai, Y., & Koike, K. (2021). Inhibition of histone methyltransferase G9a attenuates liver cancer initiation by sensitizing DNA-damaged hepatocytes to p53-induced apoptosis. Cell Death & Disease, 12(1), 1–13. https://doi.org/10.1038/s41419-020-03381-1 Cite
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IGFBPs Mediate IGF-1’s Functions in Retinal Lamination and Photoreceptor Development during Pluripotent Stem Cell Differentiation to Retinal Organoids

Researchers investigated the expression of insulin growth factor binding proteins and their role in the generation of human retinal organoids from human pluripotent stem cells.
[Stem Cells]
IGFBPs mediate IGF‐1’s functions in retinal lamination and photoreceptor development during pluripotent stem cell differentiation to retinal organoids - Zerti - - STEM CELLS - Wiley Online Library. (n.d.). Retrieved January 15, 2021, from https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.3331?af=R Cite
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Circular RNA circPSD3 Alleviates Hepatic Fibrogenesis by Regulating the miR-92b-3p/Smad7 Axis

In vitro loss-of-function and gain-of-function analyses suggested that circRNA derived from the Pleckstrin and Sec7 domain-containing 3 (circPSD3) inhibited the activation and proliferation of hepatic stellate cells.
[Molecular Therapy-Nucleic Acids]
Bu, F., Zhu, Y., Chen, X., Wang, A., Zhang, Y., You, H., Yang, Y., Yang, Y., Huang, C., & Li, J. (2021). Circular RNA circPSD3 alleviates hepatic fibrogenesis by regulating the miR-92b-3p/Smad7 axis. Molecular Therapy - Nucleic Acids, 0(0). https://doi.org/10.1016/j.omtn.2021.01.007 Cite
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Modeling Human Bile Acid Transport and Synthesis in Stem Cell-Derived Hepatocytes with a Patient-Specific Mutation

The authors developed a human induced pluripotent stem cell-based model of isogenic bile salt export pump-deficient hepatocytes in a Transwell culture system. Induced hepatocytes exhibited defects in the apical export of bile acids but maintained a low intracellular bile acid concentration by inducing basolateral export.
[Stem Cell Reports]
Hayashi, H., Osaka, S., Sakabe, K., Fukami, A., Kishimoto, E., Aihara, E., Sabu, Y., Mizutani, A., Kusuhara, H., Naritaka, N., Zhang, W., Huppert, S. S., Sakabe, M., Nakamura, T., Hu, Y.-C., Mayhew, C., Setchell, K., Takebe, T., & Asai, A. (2021). Modeling Human Bile Acid Transport and Synthesis in Stem Cell-Derived Hepatocytes with a Patient-Specific Mutation. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.12.008 Cite
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Single-Cell Analysis Reveals the Intra-Tumor Heterogeneity and Identifies MLXIPL as a Biomarker in the Cellular Trajectory of Hepatocellular Carcinoma

Researchers profiled the gene expression of single cells from human hepatocellular carcinoma (HCC) tumor and para-tumor tissues using the Smart-seq 2 sequencing method. Based on differentially expressed genes, they identified heterogeneous subclones in HCC tissues, including five HCC and two hepatocyte subclones.
[Cell Death Discovery]
Dong, X., Wang, F., Liu, C., Ling, J., Jia, X., Shen, F., Yang, N., Zhu, S., Zhong, L., & Li, Q. (2021). Single-cell analysis reveals the intra-tumor heterogeneity and identifies MLXIPL as a biomarker in the cellular trajectory of hepatocellular carcinoma. Cell Death Discovery, 7(1), 1–13. https://doi.org/10.1038/s41420-021-00403-5 Cite
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Triglycerides in Nonalcoholic Fatty Liver Disease: Guilty Until Proven Innocent

Whether and how triglycerides promote hepatocyte injury remains unclear. Consequently, it is difficult to predict whether drugs designed to reduce hepatic triglycerides will prevent the most important complications of non-alcoholic fatty liver disease.
[Trends in Pharmacological Sciences]
Semova, I., & Biddinger, S. B. (2021). Triglycerides in Nonalcoholic Fatty Liver Disease: Guilty Until Proven Innocent. Trends in Pharmacological Sciences, 0(0). https://doi.org/10.1016/j.tips.2020.12.001 Cite
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A Subset of Liver Resident Natural Killer Cells Is Expanded in Hepatitis C-Infected Patients with Better Liver Function

LMCs were less responsive to toll-like receptor stimulation than blood mononuclear cells, with fewer pro-inflammatory gene-expression pathways up-regulated after in vitro exposure to lipopolysaccharide and a TLR-7/8 agonist.
[Scientific Reports]
Doyle, E. H., Aloman, C., El-Shamy, A., Eng, F., Rahman, A., Klepper, A. L., Haydel, B., Florman, S. S., Fiel, M. I., Schiano, T., & Branch, A. D. (2021). A subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function. Scientific Reports, 11(1), 1551. https://doi.org/10.1038/s41598-020-80819-8 Cite
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Advances in Liver Cancer Stem Cell Isolation and their Characterization

Investigators review the research progress made in the isolation and characterization of liver cancer stem cells by considering a wide range of cell surface markers and sorting methods, as applied to side populations, microsphere cultures and the gradient centrifugation method.
[Stem Cell Reviews and Reports]
Liu, L., & Borlak, J. (2021). Advances in Liver Cancer Stem Cell Isolation and their Characterization. Stem Cell Reviews and Reports. https://doi.org/10.1007/s12015-020-10114-6 Cite
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Cholangiogenic Potential of Human Deciduous Pulp Stem Cell-Converted Hepatocyte-Like Cells

Stem cells from human exfoliated deciduous teeth-derived hepatocytes were intrasplenically transplanted into chronically CCl4-treated liver fibrosis model mice, followed by the analysis of donor integration and hepatobiliary metabolism in vivo.
[Current Stem Cell Research & Therapy]
Yuniartha, R., Yamaza, T., Sonoda, S., Yoshimaru, K., Matsuura, T., Yamaza, H., Oda, Y., Ohga, S., & Taguchi, T. (2021). Cholangiogenic potential of human deciduous pulp stem cell-converted hepatocyte-like cells. Stem Cell Research & Therapy, 12(1), 57. https://doi.org/10.1186/s13287-020-02113-8 Cite
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Prediction and Verification of Target of Helenalin against Hepatic Stellate Cell Activation Based on miR-200a-Mediated PI3K/Akt and NF-κB Pathways

Hepatic stellate cell (HSC)‐T6 cells were activated by interleukin-1 beta and then treated with helenalin. HSC‐T6 cells were transfected with miR-200a mimic or inhibitor, and the effect of helenalin on the miR-200a-mediated PI3K/Akt and NF-κB signaling pathways was investigated.
[International Immunopharmacology]
Fang, B., Wen, S., Li, Y., Bai, F., Wei, Y., Xiong, Y., Huang, Q., & Lin, X. (2021). Prediction and verification of target of helenalin against hepatic stellate cell activation based on miR-200a-mediated PI3K/Akt and NF-κB pathways. International Immunopharmacology, 92, 107208. https://doi.org/10.1016/j.intimp.2020.107208 Cite
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