Amniotic Fluid Stem Cells as a Novel Strategy for the Treatment of Fetal and Neonatal Neurological Diseases

Investigators outline the results of preclinical research on fetal stem cell therapy, mainly involving human amniotic fluid stem cells, in the context of perinatal neurological diseases.
[Placenta]
Abe, Y., Ochiai, D., Sato, Y., Otani, T., Fukutake, M., Ikenoue, S., Kasuga, Y., & Tanaka, M. (2021). Amniotic fluid stem cells as a novel strategy for the treatment of fetal and neonatal neurological diseases. Placenta, 104, 247–252. https://doi.org/10.1016/j.placenta.2021.01.009 Cite
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Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1

Scientists present a review focusing on studies that have used iPSCs for disease modeling and drug discovery in NPC1 and draw a comparison to commonly used NPC1 models.
[International Journal of Molecular Sciences]
Völkner, C., Liedtke, M., Hermann, A., & Frech, M. J. (2021). Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1. International Journal of Molecular Sciences, 22(2), 710. https://doi.org/10.3390/ijms22020710 Cite
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Zonal Human Hepatocytes Are Differentially Permissive to Plasmodium falciparum Malaria Parasites

To understand specific host conditions that affect infectivity, the authors studied Plasmodium falciparum parasite liver stage development in relation to the metabolic heterogeneity of fresh human hepatocytes.
[EMBO Journal]
Yang, A. S. P., van Waardenburg, Y. M., van de Vegte-Bolmer, M., van Gemert, G.-J. A., Graumans, W., de Wilt, J. H. W., & Sauerwein, R. W. (2021). Zonal human hepatocytes are differentially permissive to Plasmodium falciparum malaria parasites. The EMBO Journal, n/a(n/a), e106583. https://doi.org/10.15252/embj.2020106583 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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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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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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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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Generation of Proliferating Human Adult Hepatocytes Using Optimized 3D Culture Conditions

The authors describe optimized 3D culture conditions of primary human hepatocytes to trigger two waves of proliferation and identified matrix stiffness and cell–cell interactions as the main actors necessary for this proliferation.
[Scientific Reports]
Rose, S., Ezan, F., Cuvellier, M., Bruyère, A., Legagneux, V., Langouët, S., & Baffet, G. (2021). Generation of proliferating human adult hepatocytes using optimized 3D culture conditions. Scientific Reports, 11(1), 515. https://doi.org/10.1038/s41598-020-80019-4 Cite
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High-Fat Diet-Induced Upregulation of Exosomal Phosphatidylcholine Contributes to Insulin Resistance

The authors showed that lean mice became insulin resistant after being administered exosomes isolated from the feces of obese mice fed a high-fat diet or from patients with type II diabetes.
[Nature Communications]
Kumar, A., Sundaram, K., Mu, J., Dryden, G. W., Sriwastva, M. K., Lei, C., Zhang, L., Qiu, X., Xu, F., Yan, J., Zhang, X., Park, J. W., Merchant, M. L., Bohler, H. C. L., Wang, B., Zhang, S., Qin, C., Xu, Z., Han, X., … Zhang, H.-G. (2021). High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance. Nature Communications, 12(1), 213. https://doi.org/10.1038/s41467-020-20500-w Cite
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Histone Deacetylase 2 Regulates ULK1 Mediated Pyroptosis during Acute Liver Failure by the K68 Acetylation Site

Researchers investigated whether knockdown or pharmacological inhibition of histone deacetylase 2 could reduce the level of pyroptosis in acute liver failure (ALF) through ULK1-NLRP3-pyroptosis pathway.
[Cell Death & Disease]
Wang, Y., Chen, Q., Jiao, F., Shi, C., Pei, M., Wang, L., & Gong, Z. (2021). Histone deacetylase 2 regulates ULK1 mediated pyroptosis during acute liver failure by the K68 acetylation site. Cell Death & Disease, 12(1), 1–17. https://doi.org/10.1038/s41419-020-03317-9 Cite
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