Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Fzr1-mediated early embryo stress response impairs fetal growth and metabolic reprogramming of offspring

ABSTRACT: Stressors during early embryogenesis influence embryo developmental trajectories and have long-term metabolic effect on offspring, but the underlying mechanism remains elusive. We performed RNA-Seq to identify transcriptional differences among control and IVF embryos. Results revealed that DNA damage and the resulting activation of Fzr1 play a central role in early embryo stress responses and subsequently affect metabolic reprogramming in offspring. To investigate the underlying molecular mechanism by which Fzr1 affected embryo development and adult metabolism. We performed RNA-Seq and H3K9me3 ChIP-seq experiments to identify transcriptional and histone modification differences among control and Fzr1-OE blastocysts. To explore the underlying mechanisms of Fzr1 activation-induced metabolic disorder, we performed RNA-Seq on the subcutaneous fat tissues of 4-month-old control and Fzr1-OE mice. We further performed reduced-representation bisulfite sequencing (RRBS) of subcutaneous fat tissues to identify possible DNA methylation alterations that could potentially mediate the intergenerational transmission of the obesity phenotype. Our findings therefore provide a new perspective on the mechanisms underlying transgenerational metabolic reprogramming and will help improve offspring health.

ORGANISM(S): Mus musculus

PROVIDER: GSE182567 | GEO | 2023/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Effects of fzr1 knockdown on senescence-associated gene expression in human diploid fibroblasts.

Project description:Analysis of gene expression profile in Ras-induced senescent human diploid fibroblasts with or without depletion of fzr1/cdh1. Results provide insight into the effect on fzr1/cdh1 on the regulation of senescence-associated gene expression in human diploid fibroblasts. IMR-90-ER:Ras cells were cultured for 6 days with or without 4-hydroxytamoxifen (OHT) and were subsequently subjected to transfection with siRNA oligos against fzr1/cdh1 or control for three times (at 2 day intervals). Total RNA was isolated using Trizol reagent and were analyzed using the human 3D-Gene DNA chip (Toray) which that contains 25000 genes. The genome wide transcriptional response of proliferating cells (IMR si control2) and fzr1/cdh1 depleted senescent cells (IMR+OHT si cdh1) were compared to that of senescent cells (IMR+OHT si control).

2012-07-31 | E-GEOD-30790 | biostudies-arrayexpress

N6-methyladenosine modification of FZR1 mRNA promotes gemcitabine resistance in pancreatic cancer

Project description:Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer with limited therapeutic options, and gemcitabine insensitivity remains a major challenge. N6-methyladenosine (m6A) is a prevalent nucleotide modification in mRNA that has been linked to various biological processes in human diseases, yet its role in drug sensitivity of cancer remains largely unknown. Herein, by detecting the global m6A profile in a panel of gemcitabine-sensitive and gemcitabine-insensitive PDAC cells, we identified the key role of hyper-m6A modification of the master G0/G1 regulator Fizzy and Cell Division Cycle 20 Related 1 (FZR1) in regulating gemcitabine sensitivity. Targeting m6A modification of FZR1 improves the gemcitabine treatment response of gemcitabine-insensitive PDAC cells in vitro and in vivo. Mechanistically, Gem Nuclear Organelle Associated Protein 5 (GEMIN5) was identified as a novel m6A mediator that specifically binds to m6A-modified FZR1 and recruits the eIF3 translation initiation complex to accelerate FZR1 translation. Upregulation of FZR1 maintains the G0/G1 quiescent state and impairs gemcitabine sensitivity of PDAC cells. Further clinical analysis showed that both high levels of FZR1 m6A modification and FZR1 protein indicated a poor response to gemcitabine. These findings unveil the critical function for m6A modification in regulating gemcitabine sensitivity in PDAC and identify the m6A-FZR1 axis as a potential target to enhance gemcitabine response.

2023-06-08 | GSE206969 | GEO

N6-methyladenosine-enhanced FZR1 translation contributes to gemcitabine insensitivity in pancreatic cancer via quiescence maintenance [m6A-seq]

Project description:Herein, by detecting the global m6A profile in a panel of gemcitabine-sensitive and gemcitabine-insensitive PDAC cells, we identified the key role of hyper-m6A modification of the master G0/G1 regulator Fizzy and Cell Division Cycle 20 Related 1 (FZR1) in regulating gemcitabine sensitivity. Targeting m6A modification of FZR1 improves the gemcitabine treatment response of gemcitabine-insensitive PDAC cells in vitro and in vivo. Mechanistically, Gem Nuclear Organelle Associated Protein 5 (GEMIN5) was identified as a novel m6A mediator that specifically binds to m6A-modified FZR1 and recruits the eIF3 translation initiation complex to accelerate FZR1 translation. Upregulation of FZR1 maintains the G0/G1 quiescent state and impairs gemcitabine sensitivity of PDAC cells. Further clinical analysis showed that both high levels of FZR1 m6A modification and FZR1 protein indicated a poor response to gemcitabine.

2023-06-09 | GSE206968 | GEO

N6-methyladenosine-enhanced FZR1 translation contributes to gemcitabine insensitivity in pancreatic cancer via quiescence maintenance [PAR-CLIP-Seq]

2023-06-09 | GSE206967 | GEO

Effects of fzr1 knockdown on senescence-associated gene expression in human diploid fibroblasts.

2012-08-01 | GSE30790 | GEO

Effects of FZR1 knockout on gene expression of breast tumor cells treated with cisplatin

Project description:We knockout FZR1 in T-47D breast cancer cell line, and treated the knockout and WT cells with cisplatin. The mRNA profiles were analyze.

2020-10-05 | GSE142525 | GEO

Hepatic RNA sequence in male mice offspring conceived by in-vitro Fertilization and Frozen-thawed Embryo Transfer

Project description:Our study reported an increased risk of metabolic disorders in in-vitro Fertilization and Frozen-thawed Embryo Transfer (IVF-FET) conceived offspring compared with those born after IVF-ET. To explore the underlying mechanisms of the aberrant metabolism in male offspring conceived by IVF and FET compared with natural conceived (NC), we performed the RNA-sequencing of livers from three groups. We performed GSEA analysis. The results suggested more severe alterations in the expression of genes involved in insulin resistance pathway in the FET-chow group than that in the IVF-chow group.

2021-01-15 | GSE164819 | GEO

Expression data from 3 week old Rat liver (F1)

Project description:Developmental Origins of Health and Disease Hypothesis (DOHaD) all emphasized that maternal nutrition plays an important role on the growth and development of offspring. More and more attention has been paid on the effect of maternal high fat diet and overnutrition during pregnancy on the susceptibility of offspring metabolic diseases. So we aim to build the rat model of maternal high fat diet which may induce steatohepatitis and change of lipid metabolism in the early life of offspring, and explore their possible mechannisms.And then to investigate the influence of maternal high fat diet on the expression of hepatic metabolic genes in the early life of offspring. We used microarrays to detail the global program of gene expression underlying fatty acid liver and identified distinc distinct classes of up-regulated and down-regulated genes during this process.

2015-11-17 | GSE75079 | GEO

Alterations in hepatic gene expression and DNA methylation as underlying mechanisms of disturbed metabolism in adult mouse offspring after exposure to a prenatal high fat diet

Project description:Exposure to a prenatal high fat (HF) diet leads to an impaired metabolic phenotype in mouse offspring. The underlying mechanisms, however, are not yet fully understood. Therefore, this study investigated whether the impaired metabolic phenotype could have been mediated through altered hepatic DNA methylation and gene expression. In this study, both parent mice received a HF or low fat (LF) diet before and during pregnancy, and throughout lactation, after which offspring was weaned onto a HF diet. Previous work showed that at 12 weeks of age, the offspring displayed postprandial hypertriglyceridemia, which related to an impaired clearance of lipids from the blood into the liver after a HF meal. To study the mechanisms underlying the impaired metabolic phenotype after prenatal exposure to a HF diet, hepatic genome-wide gene expression was studied using whole transcript microarrays. In addition, hepatic DNA methylation of selected genes was assessed by bisulphite pyrosequencing.

2019-06-24 | GSE123009 | GEO

Pro-opiomelanocortin (POMC) neuron translatome signatures underlying obesogenic gestational malprogramming

Project description:Maternal unbalanced nutritional habits during embryo development and perinatal stages perturb hypothalamic neuronal programming of the offspring, thus increasing “diabesity” risk. Here we report that exposure to high-fat diet during gestation and lactation did not interfere with progeny’s hypothalamic POMC neuron specification, but significantly impaired their spatial distribution and axonal extension to target areas. Importantly, we established POMC neuron-specific translatome signatures accounting for neuronal aberrant development and axonal growth. These anatomical and molecular alterations caused metabolic dysfunction in early-life and adulthood. Our study provides fundamental insights on the molecular mechanisms underlying POMC neuron malprogramming in obesogenic contexts.

2020-02-20 | GSE135639 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data