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.
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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]
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.
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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
Using liver-specific G9a-deficient mice, scientists revealed that loss of G9a significantly attenuated liver tumor initiation caused by diethylnitrosamine.
[Cell Death & Disease]
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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
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]
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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
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]
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]
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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
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]
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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
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.
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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.
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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
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]
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