Hepatocyte-Intrinsic Type I Interferon Signaling Reprograms Metabolism and Reveals a Novel Compensatory Mechanism of the Tryptophan-Kynurenine Pathway in Viral Hepatitis

IFN-I specifically rewired tryptophan metabolism and induced hepatic tryptophan oxidation to kynurenine via Tdo2, correlating with altered concentrations of serum metabolites upon viral infection.
[PLoS Pathogens]
Lercher, A., Popa, A. M., Viczenczova, C., Kosack, L., Klavins, K., Agerer, B., Opitz, C. A., Lanz, T. V., Platten, M., & Bergthaler, A. (2020). Hepatocyte-intrinsic type I interferon signaling reprograms metabolism and reveals a novel compensatory mechanism of the tryptophan-kynurenine pathway in viral hepatitis. PLOS Pathogens, 16(10), e1008973. https://doi.org/10.1371/journal.ppat.1008973 Cite
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Identification of a Dynamic Gene Regulatory Network Required for Pluripotency Factor-Induced Reprogramming of Mouse Fibroblasts and Hepatocytes

The authors investigated the early transcriptional events of cellular reprogramming triggered by the co‐expression of Oct4, Sox2, Klf4, and c‐Myc in mouse embryonic fibroblasts and mouse hepatocytes.
[EMBO Journal]
Papathanasiou, M., Tsiftsoglou, S. A., Polyzos, A. P., Papadopoulou, D., Valakos, D., Klagkou, E., Karagianni, P., Pliatska, M., Talianidis, I., Agelopoulos, M., & Thanos, D. (2020). Identification of a dynamic gene regulatory network required for pluripotency factor-induced reprogramming of mouse fibroblasts and hepatocytes. The EMBO Journal, n/a(n/a), e102236. https://doi.org/10.15252/embj.2019102236 Cite
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Prominin-1-Radixin Axis Controls Hepatic Gluconeogenesis by Regulating PKA Activity

Investigators analyzed the levels of mRNA transcripts in serum‐starved primary WT and KO mouse hepatocytes using RNA sequencing data, and found that cyclic AMP response element‐binding protein target genes were downregulated.
[EMBO Journal]
Lee, H., Yu, D.-M., Park, J. S., Lee, H., Kim, J.-S., Kim, H. L., Koo, S.-H., Lee, J.-S., Lee, S., & Ko, Y.-G. (2020). Prominin-1-Radixin axis controls hepatic gluconeogenesis by regulating PKA activity. EMBO Reports, n/a(n/a), e49416. https://doi.org/10.15252/embr.201949416 Cite
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Targeting Hepatocyte Growth Factor/C-Mesenchymal–Epithelial Transition Factor Axis in Hepatocellular Carcinoma: Rationale and Therapeutic Strategies

The authors collected the evidence of HGF/c‐Met as a tumor progression and prognostic marker, discussed the anti‐c‐Met therapy in vitro, summarized the outcome of c‐Met inhibitors in clinical trials, and identified potential impetus for future anti‐c‐Met treatments.
[Medicinal Research Reviews]
Yu, J., Chen, G. G., & Lai, P. B. S. (n.d.). Targeting hepatocyte growth factor/c-mesenchymal–epithelial transition factor axis in hepatocellular carcinoma: Rationale and therapeutic strategies. Medicinal Research Reviews, n/a(n/a). https://doi.org/10.1002/med.21738 Cite
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Flow Enhances Phenotypic and Maturation of Adult Rat Liver Organoids

Scientists describe a rat liver organoid culture system under in vivo-like steady-state flow conditions; this system was capable of controlling the expansion and differentiation of rat liver organoids over 10 to 15 days.
[Biofabrication]
Flow enhances phenotypic and maturation of adult rat liver organoids - IOPscience. (n.d.). Retrieved October 7, 2020, from https://iopscience.iop.org/article/10.1088/1758-5090/abb538 Cite
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High-Fidelity Drug Induced Liver Injury Screen Using Human PSC-derived Organoids

Researchers established a human liver organoid (HLO) based screening model for analyzing DILI pathology at organoid resolution. HLO, generated from ten-different pluripotent stem cell lines, contained polarized immature hepatocytes with bile canaliculi-like architecture, establishing the unidirectional bile acid transport pathway.
[Gastroenterology]
Shinozawa, T., Kimura, M., Cai, Y., Saiki, N., Yoneyama, Y., Ouchi, R., Koike, H., Maezawa, M., Zhang, R.-R., Dunn, A., Ferguson, A., Togo, S., Lewis, K., Thompson, W., Asai, A., & Takebe, T. (2020). High-Fidelity Drug Induced Liver Injury Screen Using Human PSC-derived Organoids. Gastroenterology, 0(0). https://doi.org/10.1053/j.gastro.2020.10.002 Cite
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Cell Type-Specific Roles of CD38 in the Interactions of Isoniazid with NAD+ in the Liver

Because N-acetyltransferase (NAT) is expressed in hepatocytes, whereas CD38 is expressed in Kupffer cells and hepatic stellate cells, researchers explored cell type-specific roles of CD38 in the formation of a primary INH metabolite mediated isoniazid (INH)-β-nicotinamide adenine dinucleotide (NAD) as well as INH-NAD.
[Drug Metabolism and Disposition]
Zhu, J., Lu, J., Tung, H.-C., Liu, K., Li, J., Grant, D. M., Xie, W., & Ma, X. (2020). Cell type-specific roles of CD38 in the interactions of isoniazid with NAD+ in the liver. Drug Metabolism and Disposition. https://doi.org/10.1124/dmd.120.000139 Cite
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Hepatic Lipocalin 2 Promotes Liver Fibrosis and Portal Hypertension

Investigators found hepatic lipocalin 2 (LCN2) expression and serum LCN2 level markedly increased and correlated with disease severity and portal hypertension in patients with alcoholic hepatitis.
[Scientific Reports]
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Understanding Lipotoxicity in NAFLD Pathogenesis: Is CD36 a Key Driver?

Investigators provide succinct insights into the molecular mechanisms responsible for lipotoxicity in non-alcoholic fatty liver disease (NAFLD), including ER and oxidative stress, autophagy, lipoapotosis and inflammation. They highlight the role of CD36/FAT fatty acid translocase in NAFLD pathogenesis.
[Cell Death & Disease]
Rada, P., González-Rodríguez, Á., García-Monzón, C., & Valverde, Á. M. (2020). Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver? Cell Death & Disease, 11(9), 1–15. https://doi.org/10.1038/s41419-020-03003-w Cite
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Controversies Surrounding the Origin of Hepatocytes in Adult Livers and the In Vitro Generation or Propagation of Hepatocytes

The authors highlight how insights into hepatocyte regeneration and biology in vivo can inform in vitro studies to propagate primary hepatocytes with signals in liver regeneration and to generate hepatocytes de novo from pluripotent stem cells.
[Cellular and Molecular Gastroenterology and Hepatology]
Qian Pek, N. M., Liu, K. J., Nichane, M., & Ang, L. T. (2020). Controversies surrounding the origin of hepatocytes in adult livers and the in vitro generation or propagation of hepatocytes. Cellular and Molecular Gastroenterology and Hepatology. https://doi.org/10.1016/j.jcmgh.2020.09.016 Cite
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Differentiation of Cells Isolated from Afterbirth Tissues into Hepatocyte-Like Cells and Their Potential Clinical Application in Liver Regeneration

Scientists summarize the results of preclinical and clinical studies dealing with the introduction of epithelial and mesenchymal stem cells of the afterbirth origin to the liver failure therapy.
[Stem Cell Reviews and Reports]
Michalik, M., Gładyś, A., & Czekaj, P. (2020). Differentiation of Cells Isolated from Afterbirth Tissues into Hepatocyte-Like Cells and Their Potential Clinical Application in Liver Regeneration. Stem Cell Reviews and Reports. https://doi.org/10.1007/s12015-020-10045-2 Cite
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