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人多能干细胞来源肝细胞脂肪变性模型的建立。

Modeling human hepatic steatosis in pluripotent stem cell-derived hepatocytes.

机构信息

University/BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh BioQuarter, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.

Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh BioQuarter, 5 Little France Crescent, Edinburgh EH16 4UU, UK.

出版信息

STAR Protoc. 2021 Apr 21;2(2):100493. doi: 10.1016/j.xpro.2021.100493. eCollection 2021 Jun 18.

DOI:10.1016/j.xpro.2021.100493
PMID:33997813
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8091923/
Abstract

This protocol describes the production of hepatocyte-like cells (HLCs) from human pluripotent stem cells and how to induce hepatic steatosis, a condition characterized by intracellular lipid accumulation. Following differentiation to an HLC phenotype, intracellular lipid accumulation is induced with a steatosis induction cocktail, allowing the user to examine the cellular processes that underpin hepatic steatosis. Furthermore, the renewable nature of our system, on a defined genetic background, permits in-depth mechanistic analysis, which may facilitate therapeutic target identification in the future. For complete details on the use and execution of this protocol, please refer to Sinton et al. (2021).

摘要

本方案描述了从人类多能干细胞生成肝样细胞(HLC)的方法,以及如何诱导肝脂肪变性,即细胞内脂质积累的一种病症。在分化为 HLC 表型后,用脂肪变性诱导混合物诱导细胞内脂质积累,从而可以检查支持肝脂肪变性的细胞过程。此外,在定义的遗传背景下,我们的可再生系统允许进行深入的机制分析,这有助于将来确定治疗靶点。如需详细了解本方案的使用和实施,请参考 Sinton 等人(2021 年)的文献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/9c751fc743bc/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/f14951a84a20/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/c6f5df187696/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/249e294d1536/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/750acedeb437/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/90e871e2462d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/55a33e131e47/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/9c751fc743bc/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/f14951a84a20/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/c6f5df187696/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/249e294d1536/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/750acedeb437/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/90e871e2462d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/55a33e131e47/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc6f/8091923/9c751fc743bc/gr6.jpg

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本文引用的文献

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Mathematical modelling of oxygen gradients in stem cell-derived liver tissue.基于干细胞的肝组织中氧梯度的数学建模。
PLoS One. 2021 Feb 8;16(2):e0244070. doi: 10.1371/journal.pone.0244070. eCollection 2021.
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A human pluripotent stem cell model for the analysis of metabolic dysfunction in hepatic steatosis.一种用于分析肝脂肪变性中代谢功能障碍的人类多能干细胞模型。
iScience. 2020 Dec 11;24(1):101931. doi: 10.1016/j.isci.2020.101931. eCollection 2021 Jan 22.
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Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells.
性激素对肝功能及疾病的影响。
Cells. 2023 Jun 11;12(12):1604. doi: 10.3390/cells12121604.
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Dimethyl fumarate reduces hepatocyte senescence following paracetamol exposure.富马酸二甲酯可减轻对乙酰氨基酚暴露后肝细胞的衰老。
iScience. 2021 May 19;24(6):102552. doi: 10.1016/j.isci.2021.102552. eCollection 2021 Jun 25.
双酚A、F和S在人干细胞来源的肝样细胞中诱导的全基因组表达变化。
EXCLI J. 2020 Nov 4;19:1459-1476. doi: 10.17179/excli2020-2934. eCollection 2020.
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Development of a cost-effective automated platform to produce human liver spheroids for basic and applied research.开发一种具有成本效益的自动化平台,用于生产用于基础和应用研究的人类肝球体。
Biofabrication. 2020 Oct 28;13(1). doi: 10.1088/1758-5090/abbdb2.
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Multiomics Analyses of HNF4α Protein Domain Function during Human Pluripotent Stem Cell Differentiation.人类多能干细胞分化过程中HNF4α蛋白结构域功能的多组学分析
iScience. 2019 Jun 28;16:206-217. doi: 10.1016/j.isci.2019.05.028. Epub 2019 May 24.
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Semi-automated Production of Hepatocyte Like Cells from Pluripotent Stem Cells.从多能干细胞半自动生产类肝细胞
J Vis Exp. 2018 Jul 27(137):57995. doi: 10.3791/57995.
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Modelling non-alcoholic fatty liver disease in human hepatocyte-like cells.在人源肝样细胞中建立非酒精性脂肪性肝病模型。
Philos Trans R Soc Lond B Biol Sci. 2018 Jul 5;373(1750). doi: 10.1098/rstb.2017.0362.
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