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Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE131806 | GEO | 2022/03/04

REPOSITORIES: GEO

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Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging [FigS3]

Project description:Although aging associated decline of liver regeneration was discovered half a century ago, how aging contributes to the decline of liver regenerative capacity and how to improve this capacity in the elderly is still unknown. Hepatocyte plasticity is known to play a central role in the maintenance of liver regeneration; hence, we describe a strategy to explore the mechanisms underlying the relation between aging and hepatocyte plasticity: experiments with human induced-pluripotent-stem-cell–derived hepatocytes (hiPSC-Heps). Here, we established a simple and convenient method for generation of hiPSC-Heps that can maintain hepatic function for a long time with gradual accumulation of aging related markers and characteristics. We found that in contrast to rodent hepatocytes, FGF2 is essential for the plasticity of human hepatocytes, and the FGF2-activated MAPK–EZH2 axis can help to reprogram hiPSC-Heps into proliferative hepatic cells with a bipotential differentiation ability. Notably, our results showed the plasticity of hiPSC-Heps decreases with aging and this phenomenon strongly correlates with histone acetylation. Moreover, we found that selective inhibition of histone deacetylases can markedly improve the plasticity of old hiPSC-Heps and primary human hepatocytes and surprisingly increases the repopulation capacity of old PHHs in a liver injury model. Therefore, we can conclude that aging-associated histone hypoacetylation impairs hepatocyte plasticity.

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Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging [Fig4]

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Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging [Fig1, FigS1 and Fig3]

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Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging

Project description:Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging

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Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging [FigS3]

Project description:Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging [FigS3]

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Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging [Fig4]

Project description:Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging [Fig4]

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