Epigenetic compensation promotes liver regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA514869 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8437290_1.fastq.gz | Fastqsanger.gz | |||
| SRR8437290_2.fastq.gz | Fastqsanger.gz | |||
| SRR8437300_1.fastq.gz | Fastqsanger.gz | |||
| SRR8437300_2.fastq.gz | Fastqsanger.gz | |||
| SRR8437310_1.fastq.gz | Fastqsanger.gz |
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Project description: Not available
| S-EPMC6615735 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-05-31 | GSE125008 | GEO
Project description:Liver regeneration is critical for maintaining whole-body homeostasis, especially under the exposure to deadly chemical toxins. Understanding the molecular mechanisms underlying liver repair is critical for the development of intervention strategies to treat liver diseases. In this study, we identified ubiquitin-specific Proteases 42 (USP42) as a novel deubiquitinases (DUB) of peroxisome proliferators-activated receptor γ (PPARγ) in hepatocytes. This DUB interacted, deubiquitinated and stabilized PPARγ, and increased PPAR targeted proliferative and anti-oxidative gene expressions, which protects liver from carbon tetrachloride (CCL4) induced oxidative injury and promotes liver regeneration. In addition, fibroblast growth factor 2 (FGF2) initiated USP42 expression and enhanced the interaction between USP42 and PPARduring liver regeneration process. Moreover, the PPARfull agonist, rosiglitazone (RSG), possesses the ability to further reinforce the USP42-PPARinterplay, which enlightens us to construct an extracellular vesicle-based targeting strategy to activate liver USP42-PPAR axis and promote liver regeneration. In summary, our work uncovers the importance of USP42-PPAR axis mediated liver tissue homeostasis, and provides a promising regimen to target this protein-protein interplay for liver regeneration.
2025-01-15 | GSE286997 | GEO
Project description:Mammalian tissues have a limited regenerative capacity. Previous studies showed that dedifferentiation contributes to tissue regeneration in non-mammalian vertebrate species such as zebrafish and newt. However, dedifferentiation is rarely observed in mammalian tissues even in the neonatal stage and therefore artificial induction of dedifferentiation might enhance regeneration in mammalian tissues. Here we demonstrate that short-term expression of Yamanaka 4 factors (4F) induces dedifferentiation and proliferation in the liver by using lineage-traceable, hepatocyte-specific 4F inducible mouse model. Global transcriptome analysis shows that 4F expression transiently reduces the expression of hepatic-lineage markers and induces the expression of a large set of proliferative markers and epigenetic modifiers along with global epigenetic changes as assessed by DNA-accessibility analysis. More importantly, lineage-tracing experiments showed that 4F-expressing hepatocytes acquire liver stem/progenitor cell markers, suggesting that 4F induces partial reprogramming. Moreover, 4F enhances MyoD-mediated transdifferentiation in the liver, suggesting that 4F endows hepatocytes with plasticity. Lastly, 4F expression attenuated liver injury associated with more proliferative capacity and better survival rate, indicating that 4F enhances liver regeneration. Taken together, these results demonstrate that liver-specific 4F expression induces dedifferentiation and promotes liver regeneration.
2022-04-27 | GSE144600 | GEO
Project description:The liver is the only organ in mammals, which fully regenerates after injury. To identify novel regulators of liver regeneration, we performed quantitative large-scale proteomics analysis of subcellular fractions from normal versus regenerating mouse liver. Proteins of the ubiquitin-proteasome pathway were rapidly regulated by partial hepatectomy, with the ubiquitin ligase Nedd4-1 being among the top hits. Knock-down of Nedd4-1 in hepatocytes in vivo through nanoparticle-mediated delivery of siRNA caused severe liver damage after partial hepatectomy and impaired regeneration, resulting in liver failure. Mechanistically, we demonstrate that Nedd4-1 is required for efficient activation of Erk1/2 signaling by receptor tyrosine kinases involved in liver regeneration through inhibition of receptor internalization, thus controlling a major pro-mitogenic and cytoprotective signaling pathway in the regenerating liver. These results highlight the power of large-scale proteomics to identify key players in liver regeneration and the importance of posttranslational regulation of growth factor signaling in this process.
2017-09-13 | PXD004108 | Pride
Project description:SOCS2 Ensures Metabolic Function and Mass Restoration During Liver Regeneration - SOCS2 plays distinct and contrasting roles during liver regeneration. Early after injury, SOCS2 expression increases and limits the rate of regeneration, preserving metabolic activity. Surprisingly, at later times, the role of SOCS2 reverses to promote liver regeneration by stimulating GH release from the pituitary via effects on serum levels of insulin-like growth factor 1. Loss of SOCS2 promotes GH signaling by increasing growth hormone receptor levels and driving phosphorylation of proteins in the GH pathway, establishing a state of hyper-responsiveness to GH. These findings suggest a single protein can play contrasting roles at different times after liver injury and modulation of GH signaling achieves an optimal rate of liver regeneration to balance metabolic and restorative needs. To further understand the mechanism by which SOCS2 increases early liver regeneration, we performed microarray analysis of Socs2-null mice wildtype mice at 24 and 36 hours after hepatectomy. C57BL/6 mice where used as wildtype controls. Socs2-null animals were maintained on a C57BL/6 background. Both wildtype and Socs2-null adult mice were subjected to 2/3 hepatectomy and liver tissue isolated at 24 hours and 36 hours post hepatectomy. Time zero was without hepatectomy in age-matched mice for each genotype. Total RNA isolated from collected liver tissues was pooled for three animals at each time point and two biological replicates (3 pooled liver RNAs each) were labeled for array analysis. This results in a total of 12 microarrays.
2014-02-01 | E-GEOD-51801 | biostudies-arrayexpress
Project description:Robust liver regeneration counteracts and facilitates a recovery from liver injuries. The underlying epigenetic mechanisms, however, are not fully appreciated. In the present study we investigated the role of suppressor of variegation 3-9 homolog 1 (Suv39h1), a histone H3K9 methyltransferase, in liver regeneration. Suv39h1 expression was repressed by DNMT1 during liver regeneration. Systemic or hepatocyte-specific deletion of Suv39h1 in mice enhanced liver regeneration and post-surgery survival following partial hepatectomy. RNA sequencing revealed high-mobility group protein B2 (HMGB2) as a target for Suv39h1. Suv39h1 down-regulation in proliferating hepatocytes allowed E2F1 to activate HMGB2 transcription. Consistently, HMGB2 knockdown attenuated proliferation of hepatocytes in response to HGF treatment and suppressed liver regeneration in mice. Integrated transcriptomic analysis indicated that HMGB2 might contribute to proliferation of hepatocytes by regulating a panel of pro-regenerative genes. Importantly, Suv39h1 inhibition by chaetocin boosted liver regeneration in mice. Finally, significant correlation between Suv39h1, HMGB2, and proliferative markers was identified in patients with acute liver failure. In conclusion, our data uncover an unrecognized role for Suv39h1 in liver regeneration. Therefore, targeting Suv39h1 may be considered as a viable strategy to boost liver regeneration after injury.
2026-05-15 | GSE313427 | GEO
Project description:Robust liver regeneration counteracts and facilitates a recovery from liver injuries. The underlying epigenetic mechanisms, however, are not fully appreciated. In the present study we investigated the role of suppressor of variegation 3-9 homolog 1 (Suv39h1), a histone H3K9 methyltransferase, in liver regeneration. Suv39h1 expression was repressed by DNMT1 during liver regeneration. Systemic or hepatocyte-specific deletion of Suv39h1 in mice enhanced liver regeneration and post-surgery survival following partial hepatectomy. RNA sequencing revealed high-mobility group protein B2 (HMGB2) as a target for Suv39h1. Suv39h1 down-regulation in proliferating hepatocytes allowed E2F1 to activate HMGB2 transcription. Consistently, HMGB2 knockdown attenuated proliferation of hepatocytes in response to HGF treatment and suppressed liver regeneration in mice. Integrated transcriptomic analysis indicated that HMGB2 might contribute to proliferation of hepatocytes by regulating a panel of pro-regenerative genes. Importantly, Suv39h1 inhibition by chaetocin boosted liver regeneration in mice. Finally, significant correlation between Suv39h1, HMGB2, and proliferative markers was identified in patients with acute liver failure. In conclusion, our data uncover an unrecognized role for Suv39h1 in liver regeneration. Therefore, targeting Suv39h1 may be considered as a viable strategy to boost liver regeneration after injury.
2026-05-15 | GSE313425 | GEO
Project description:Robust liver regeneration counteracts and facilitates a recovery from liver injuries. The underlying epigenetic mechanisms, however, are not fully appreciated. In the present study we investigated the role of suppressor of variegation 3-9 homolog 1 (Suv39h1), a histone H3K9 methyltransferase, in liver regeneration. Suv39h1 expression was repressed by DNMT1 during liver regeneration. Systemic or hepatocyte-specific deletion of Suv39h1 in mice enhanced liver regeneration and post-surgery survival following partial hepatectomy. RNA sequencing revealed high-mobility group protein B2 (HMGB2) as a target for Suv39h1. Suv39h1 down-regulation in proliferating hepatocytes allowed E2F1 to activate HMGB2 transcription. Consistently, HMGB2 knockdown attenuated proliferation of hepatocytes in response to HGF treatment and suppressed liver regeneration in mice. Integrated transcriptomic analysis indicated that HMGB2 might contribute to proliferation of hepatocytes by regulating a panel of pro-regenerative genes. Importantly, Suv39h1 inhibition by chaetocin boosted liver regeneration in mice. Finally, significant correlation between Suv39h1, HMGB2, and proliferative markers was identified in patients with acute liver failure. In conclusion, our data uncover an unrecognized role for Suv39h1 in liver regeneration. Therefore, targeting Suv39h1 may be considered as a viable strategy to boost liver regeneration after injury.
2026-05-15 | GSE313198 | GEO
Project description:Receptor tyrosine kinases MET and EGFR are critically involved in initiation of liver regeneration. Other cytokines and signaling molecules also help in the early part of the process. Regeneration employs effective redundancy schemes to compensate for missing signals. Elimination of any single signaling pathway only delays but does not abolish the process. Our present study, however, shows that combined systemic elimination of MET and EGFR signaling abolishes liver regeneration, prevents restoration of liver mass and leads to liver decompensation. Our results demonstrate that liver function is dependent on synchronous availability of signaling from these two pathways. The study shows that MET and EGFR separately control many non-overlapping signaling endpoints, allowing for compensation when only one of the signals is blocked. The combined elimination of the signals however was not tolerated. The results provide critical new information on interactive MET and EGFR signaling and the contribution of their combined absence to regeneration arrest and liver decompensation. We used microarrays to detail the global programme of gene expression in METKO-canertinib mouse liver following a partial hepatectomy
2016-10-27 | GSE77867 | GEO