Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene repression through epigenetic modulation by PPARA enhances hepatocellular proliferation

ABSTRACT: Peroxisome proliferator-activated receptor α (PPARA) is a key mediator of lipid metabolism and inflammation. Activation of PPARA in rodents causes hepatocyte proliferation, but the underlying mechanism is poorly understood. This study focused on genes repressed by PPARA and analyzed the mechanism by which PPARA promotes hepatocyte proliferation in mice. Activation of PPARA by agonist treatment was autoregulated, and induced expression of the epigenetic regulator UHRF1 via activation of the newly described PPARA target gene E2f8, that in turn regulates Uhrf1. UHRF1 strongly repressed expression of CDH1 via methylation of the Cdh1 promoter marked with H3K9me3. Repression of CDH1 by PPARA activation was reversed by PPARA deficiency or knockdown of E2F8 or UHRF1. Furthermore, forced expression of CDH1 inhibited expression of the Wnt signaling target genes such as Myc after PPARA activation, and suppressed hepatocyte hyperproliferation. These results demonstrate that the PPARA-E2F8-UHRF1-CDH1 axis causes epigenetic regulation of hepatocyte proliferation. This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE154277 | GEO | 2022/04/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genome-wide profiling of PPARA in PPARA agonist-treated mouse livers [ChIP-seq]

Project description:To clarify mouse PPARA autoinduction and hepatocyte proliferation signaling pathways, genome-wide distribution of PPARA in the liver of PPARA agonist-treated mice compared to Vehicle was analyzed.

2022-04-05 | GSE154276 | GEO

Wnt Signaling Regulates Hepatocyte Cell Division by a Transcriptional Repressor Cascade

Project description:Cell proliferation is tightly controlled by inhibitors that block cell cycle progression until growth signals relieve this inhibition, allowing cells to divide. In several tissues including the liver, cell proliferation is inhibited at mitosis by the transcriptional repressors E2F7 and E2F8, leading to formation of polyploid cells. Whether growth factors promote mitosis and cell cycle progression by relieving the E2F7/E2F8-mediated inhibition is unknown. We report here on a new mechanism of cell division control in the postnatal liver, in which Wnt/βcatenin signaling maintains active hepatocyte cell division through Tbx3, a Wnt target gene. Tbx3 directly represses transcription of E2F7 and E2F8, thereby promoting mitosis. This cascade of sequential transcriptional repressors, initiated by Wnt signals, provides a new paradigm for exploring how commonly active developmental signals impact cell cycle completion.

2022-07-02 | GSE205339 | GEO

Global hepatic gene expression data from PPARa liver-specific KO and PPARa liver wild-type male mice fed ad libitum

Project description:To identify genes whose expression is under the strict dependence of hepatocyte PPARa activity, we used a mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to their liver WT littermates (albumin-Cre-/- Pparaflox/flox or LWT) fed ad libitum or fasted for 24 hours.

2017-12-16 | GSE96559 | GEO

Global hepatic gene expression data from PPARa liver KO, PPARa liver WT, PPARaKO and WT male mice treated or not with Fenofibrate

2016-02-20 | GSE73298 | GEO

Global hepatic gene expression data from PPARa liver KO, PPARa liver WT, PPARaKO and WT male mice fed ad libitum, fasted for 24 hours and re-fed

Project description:If the function of the nuclear receptor PPARa is well-known during a prolongated fasting, its hepatic biological function during feeding and refeeding conditions still needs to be investigated. Moreover, in vivo data collected so far on PPARa function during fasting were obtained using the total Ppara KO transgenic mouse model. To identify genes whose expression is under the strict dependence of hepatic PPARa activity, we generated a new mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to total Ppara KO (KO), wild-type (WT) and liver WT (albumin-Cre-/- Pparaflox/flox or LWT) mice under three nutritional challenges. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice fed ad libitum, fasted for 24 hours and refed.

2016-02-20 | GSE73299 | GEO

Global hepatic gene expression data from PPARa liver KO, PPARa liver WT, PPARaKO and WT male mice treated or not with Fenofibrate

Project description:Fenofibrate is a specific agonist of the nuclear receptor PPARa. To identify the gene expression under the strict dependence of hepatic PPARa activity, we generated a new mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to total Ppara KO (KO), wild-type (WT) and liver WT (albumin-Cre-/- Pparaflox/flox or LWT) mice. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice. There are 36 liver samples, each from an individual mouse. The samples are from Ppara liver KO (LKO), Ppara KO (KO), wild-type (WT) and liver WT (LWT) male mice of 14 week-old from the same genetic background (C57Bl/6J) treated with Fenofibrate (100 mg/kg/day) or vehicle (aqueous solution of gum Arabic 3%) by daily gavage for 10 days. n= 4 mice for LKO, LWT and WT genotypes treated with vehicle; n=3 for KO mice treated with vehicle; n=5 mice for LWT, LKO and KO genotypes treated with fenofibrate; n=4 WT mice treated with fenofibrate. All mice were sacrified at ZT14.

2016-02-20 | E-GEOD-73298 | biostudies-arrayexpress

Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth [bulk RNA-seq]

Project description:Mechanisms underlying human hepatocyte growth in development and regeneration are incompletely understood. In vitro, human fetal hepatocytes (FH) can be robustly grown as organoids, while adult primary human hepatocyte (PHH) organoids remain difficult to expand, suggesting different growth requirements between fetal and adult hepatocytes. Here, we characterize hepatocyte organoid outgrowth using temporal transcriptomic and phenotypic approaches. FHs initiate reciprocal transcriptional programs involving increased proliferation and repressed lipid metabolism upon initiation of organoid growth. We exploited these insights to design maturation conditions for FH organoids, resulting in acquisition of mature hepatocyte morphological traits and increased expression of functional markers. During PHH organoid outgrowth in the same culture condition, the adult transcriptomes initially mimic the fetal transcriptomic signatures, but PHHs rapidly acquire disbalanced proliferation-lipid metabolism dynamics, resulting in steatosis and halted organoid growth. IL6 supplementation, as emerged from the fetal dataset, and simultaneous activation of the metabolic regulator FXR, prevents steatosis and promotes PHH proliferation, resulting in improved expansion of the derived organoids. Single-cell RNA sequencing analyses reveal preservation of their fetal and adult hepatocyte identities in the respective organoid cultures. Our findings uncover mitogen requirements and metabolic differences determining proliferation of hepatocytes changing from development to adulthood.

2024-04-30 | GSE264260 | GEO

Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth [scRNA-seq]

2024-04-30 | GSE264261 | GEO

Uhrf1 control the proliferation and the differentiation of satellite cells [MBD-seq]

Project description:DNA methylation is an essential epigenetic regulation for cellular identity. In muscle stem cells, termed satellite cells, DNA methylation patterns are dynamically changed during muscle regeneration. However, how these DNA methylation patterns are maintained remain unclear. Here, we demonstrate that a key epigenetic regulator Uhrf1 (ubiquitin-like with PHD and RING finger domains 1) is activated in proliferating but not expressed in quiescent or differentiated satellite cells. Ablation of Uhrf1 in satellite cell impairs the proliferation and differentiation of satellite cells, leading to failure of muscle regeneration. Loss of Uhrf1 in satellite cells alters transcriptional programs and leads to DNA hypomethylation with the activation of Cdkn1a and Notch signalling. Down-regulation of Cdkn1a and Notch signalling rescued the proliferation and differentiation defect in Uhrf1-deficient satellite cells. Therefore, this study suggest that Uhrf1 can regulate the self-renewal and differentiation of satellite cells through DNA methylation patterning.

2022-02-04 | GSE169184 | GEO

Uhrf1 control the proliferation and the differentiation of satellite cells [RNA-Seq]

2022-02-04 | GSE169192 | GEO