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Status |
Public on Mar 04, 2022 |
Title |
Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging [FigS3] |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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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Overall design |
Transcriptome profiling of hiPSC derived Heptocyte (D22-Hep, D52-Hep and D72-Hep), D22-pHC, PHHs and PHH-pHC
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Contributor(s) |
NIE Y, Zheng Y, Taniguchi H |
Citation missing |
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Submission date |
May 28, 2019 |
Last update date |
Mar 06, 2022 |
Contact name |
Yun-Zhong NIE |
E-mail(s) |
yznie@yokohama-cu.ac.jp
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Organization name |
Yokohama City University Graduate School of Medicine
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Department |
Department of Regenerative Medicine
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Lab |
Hideki Taniguchi
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Street address |
3-9, Fukuura, Kanazawa-ku
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City |
YOKOHAMA |
State/province |
Kanagawa |
ZIP/Postal code |
236-0004 |
Country |
Japan |
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Platforms (1) |
GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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Samples (2) |
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This SubSeries is part of SuperSeries: |
GSE131806 |
Histone Hypoacetylation Impairs the Plasticity of Human Hepatocytes with Aging |
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Relations |
BioProject |
PRJNA545037 |