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| Status |
Public on Aug 05, 2023 |
| Title |
Matrix stiffness modulates fibrogenesis in hepatic stellate cells through AP-1-induced chromatin priming [ATAC-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The increased stiffness of the extracellular matrix is a key driver of liver fibrosis. The activated hepatic stellate cell (HSC) is the major producer of extracellular matrix (ECM) components. While little is known about the epigenomic changes that underlie the fibrogenic impact of ECM mechanics. In this study, we utilized a reliable in vitro system to mimic liver cirrhosis and integrated multi-omics analysis, which includes time-series RNA-seq and ATAC-seq as well as histone modification Cut&Tag, with imaging and biochemical essays to study the mechanism underlying the biomechanics function on fibrotic phenotype. We found that cells cultured in stiff matrix displayed more accessible chromatin sites, consisting of amount regions became accessible before stable fibrotic phenotype. We defined these regions as primed chromatin that chromatin accessibility foreshadows changes in gene expression. This kind of chromatin enriched in cytoskeleton organization and responding to mechanical stimulus biological process. Here, we depicted the AP-1 transcription factor family as being responsible for driving the construction of primed chromatin. Among AP-1 transcription factors, we confirmed JUN was critical to reconstruct chromatin accessibility to promote fibrogenic genotype. In addition, we described ERK contribute to the activation of JUN resulting in its binding on chromatin. Our results profiled a dynamic landscape of chromatin accessibility and defined the primed chromatin that contribute to fibrosis during responding to stiff matrix. We identified that AP-1 was capable of reorganizing the chromatin accessibility in mechanotransduction.
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| Overall design |
ATAC-seq (Assay for Transposase-Accessible Chromatin with high throughput sequencing) analysis of LX-2 cell line cultured in stiff with or without the expresison of JUN-AA. ATAC-seq analysis of LX-2 cell line cultured in soft with or without the expression of JUN-EE.
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| Contributor(s) |
Yuan W, Zhao W |
| Citation missing |
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| |
| Submission date |
Aug 04, 2023 |
| Last update date |
Aug 05, 2023 |
| Contact name |
Wenxue Zhao |
| E-mail(s) |
zhaowenxue@stu.pku.edu.cn
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| Organization name |
Peking University
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| Street address |
Yiheyuan Road
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| City |
Beijing |
| ZIP/Postal code |
100871 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE220703 |
Matrix stiffness modulates fibrogenesis in hepatic stellate cells through AP-1-induced chromatin priming |
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| Relations |
| BioProject |
PRJNA1002239 |
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