Gene expression differences in yolk sac tissue between wild-type and Zfp36l3 knockout mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE66138 | GEO | 2016/05/05
SECONDARY ACCESSION(S): PRJNA275943
REPOSITORIES: GEO
Similar Datasets
Project description:The ZFP36L3 protein is a rodent-specific, placenta- and yolk sac-specific member of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins. These proteins bind to AU-rich elements in target mRNAs, and promote their deadenylation and decay. Mice deficient in ZFP36L3 exhibited decreased neonatal survival rates, but no apparent morphological changes in the placenta or surviving offspring. Zfp36l3 is paternally imprinted, with profound parent-of-origin effects on gene expression. RNASeq of KO placental mRNA revealed many significantly affected transcripts, some of which exhibited decreased decay rates in differentiated trophoblast stem cells derived from KO blastocysts. The type 1 transferrin receptor mRNA was unexpectedly decreased in KO placentas, despite an increase in its stability. This receptor is critical for placental iron uptake from the maternal circulation, and its decrease was accompanied by decreased iron stores in the KO fetus, suggesting that this intrauterine deficiency might have deleterious consequences in later life.
2016-05-05 | GSE66137 | GEO
Project description:The ZFP36L3 protein is a rodent-specific, placenta- and yolk sac-specific member of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins. These proteins bind to AU-rich elements in target mRNAs, and promote their deadenylation and decay. We addressed the hypotheses that the absence of ZFP36L3 would result in the accumulation of target transcripts in placenta and/or yolk sac, and that some of these would be important for female reproductive physiology and overall fecundity. Mice deficient in ZFP36L3 exhibited decreased neonatal survival rates, but no apparent morphological changes in the placenta or surviving offspring. We found Zfp36l3 to be paternally imprinted, with profound parent-of-origin effects on gene expression. The protein was highly expressed in the syncytiotrophoblast cells of the labyrinth layer of the placenta, and the epithelial cells of the yolk sac. RNA-Seq of placental mRNA from Zfp36l3 KO mice revealed many significantly up-regulated transcripts, whereas there were few changes in KO yolk sacs. Many of the up-regulated placental transcripts exhibited decreased decay rates in differentiated trophoblast stem cells derived from KO blastocysts. Several dozen transcripts were deemed high probability targets of ZFP36L3; these include proteins known to be involved in trophoblast and placenta physiology. The type 1 transferrin receptor mRNA was unexpectedly decreased in KO placentas, despite an increase in its stability in KO stem cells. This receptor is critical for placental iron uptake, and its decrease was accompanied by decreased iron stores in the KO fetus, suggesting that this intrauterine deficiency might have deleterious consequences in later life.
2016-04-19 | GSE79767 | GEO
Project description:In this study, we identify SYDE1 as a novel GCM1 target gene. We demonstrate that SYDE1 promotes placental cell migration and invasion and that the GCM1-SYDE1 axis is crucial for placental development. Importantly, retarded placental and fetal growth with defective spongiotrophoblast layer, compromised vasculogenesis, and abnormal maternal-trophoblast interface are noted in the Syde1 homozygous knockout (KO) placenta. Along this line, decreased SYDE1 expression is observed in human IUGR placentas. We further demonstrated that components of the renin-angiotensin system (RAS) and Syde2 are differentially expressed in Syde1-KO placenta, which might contribute to normal neonatal delivery in Syde1-KO mothers
2016-10-18 | GSE81468 | GEO
Project description:Background: Maternal iron deficiency (ID) is associated with poor pregnancy and fetal outcomes. The effect is thought to be mediated by the placenta but there is no comprehensive assessment of placental response to maternal ID. Additionally, whether the influence of maternal ID on the placenta differs by fetal sex is unknown. Objectives: Our primary aim was to identify gene and protein signatures of ID mouse placentas at mid-gestation. A secondary objective was to profile the expression of iron genes in mouse placentas across gestation. Methods: We used a real-time PCR based array to determine the mRNA expression of all known iron genes in mouse placentas at embryonic day (E) 12.5, E14.5, E16.5, and E19.5 (n=3 placentas/time point). To determine the effect of maternal ID, we performed RNA sequencing and proteomics in male and female placentas from ID and iron adequate mice at E12.5 (n=8 dams/diet). Results: In female placentas, six genes including transferrin receptor (Tfrc) and solute carrier family 11 member 2 were significantly changed by maternal ID. An additional 154 genes were altered in male ID placentas. Proteomic analysis quantified 7662 proteins in the placenta. Proteins translated from iron responsive element (IRE) containing mRNAs were altered in abundance; ferritin and ferroportin 1 decreased while TFRC increased in ID placenta. Less than 4% of the significantly altered genes in ID placentas occurred both at the transcriptional and translational levels. Conclusions: Our data demonstrate that the impact of maternal ID on placental gene expression in mice is limited in scope and magnitude at mid-gestation. We provide strong evidence for IRE-based transcriptional and translational coordination of iron gene expression in the mouse placenta. Finally, we discover sexually dimorphic effects of maternal ID on placental gene expression, with more genes and pathways altered in male compared with female mouse placentas.
2021-03-12 | PXD023454 | Pride
Project description:Tristetraprolin is a vertebrate CCCH tandem zinc finger protein that can bind to and destabilize certain mRNAs containing AU-rich element binding sites. zfs1 is the single gene in the fission yeast, Schizosaccharomyces pombe, that encodes a protein containing the critical features of the tristetraprolin zinc finger domain. zfs1 has been linked to pheromone signal transduction control and to the coordination of mitosis, but no biological function has been ascribed to the zfs1 protein. Through a functional genomics approach we compared transcript levels in wild-type and zfs1-deficient S. pombe strains; those elevated in the zfs1-deficient strain were examined for the presence of potential tristetraprolin-like binding sites. One such potential target transcript was encoded by arz1, a gene encoding a protein of unknown function that contains armadillo repeats. arz1 mRNA decay was inhibited in the zfs1-deficient strain when it was expressed under the control of a thiamine-repressible promoter. Mutations within one AU-rich element present in the arz1 3prime-untranslated region protected this transcript from zfs1-promoted decay, whereas mutating another potential binding site had no effect. Binding assays confirmed a direct interaction between zfs1 and arz1 mRNA-based probes; this interaction was eliminated when key residues were mutated in either zfs1 zinc finger. zfs1 and its targets in S. pombe represent a useful model system for studies of zinc finger protein/AU-rich element interactions that result in mRNA decay. Experiment Overall Design: S. pombe wild-type and zfs1-deficient strains were grown to 1.0 A600 in EMM+5S at 30C for steady state analysis. Total cellular RNA was prepared from four replicate cultures.
2008-06-15 | E-GEOD-8122 | biostudies-arrayexpress
Project description:Basophils play crucial roles in type 2 immune responses, such as chronic allergic inflammation and protective immunity against parasites. However, the molecular mechanisms regulating basophil activation and effector molecule production remain poorly understood. To investigate the role of RNA-binding proteins (RBPs), we first analyzed the gene expression of CCCH zinc finger proteins in antigen/IgE-stimulated basophils. Among these proteins, we identified that Zfp36, encoding tristetraprolin (TTP), was the most significantly upregulated gene. Therefore, we focused on the functions of TTP in basophils. We generated TTP-KO mice using the CRISPR-Cas9 method and conducted bulk RNA-seq analysis of antigen/IgE-stimulated basophils from wild-type (WT) and TTP-knockout (TTP-KO) mice. TTP-KO basophils exhibited elevated mRNA expression of pro-inflammatory mediators, such as Il4, Il13, Areg, Ccl3, and Cxcl2, compared to WT basophils. These data suggest that TTP is a key regulator of basophil activation, controlling the mRNA expression of inflammatory mediators.
2024-11-17 | GSE272532 | GEO
Project description:The placenta serves as the structural interface for nutrient and waste exchange for proper fetal development. Although defects in placental function result in various placental disorders, molecular mechanisms orchestrating placental development and function are poorly understood. Gene targeting studies have shown that Hgf or c-Met KO embryos exhibit growth retardation and markedly smaller size of the placenta, and die by E14.5. Stem/progenitor cells in various tissues express c-Met and they participate in morphogenesis and tissue repair. Thus, we hypothesized that the HGF/c-Met signaling pathway is essential for the emergence, proliferation, and/or differentiation of putative stem/precursor cells of labyrinth trophoblasts at the midgestation stage. To examine the downstream mechanisms of HGF/c-Met signaling pathway that regulate placental labyrinth development, we performed microarray analysis and compared the transcriptional profiles of wild-type and c-Met g-KO placentas. The highly enriched gene ontology categories among the transcripts that were down-regulated in the mutant placentas were related to cell cycle, transcription, and placenta development. Surprisingly, the most highly enriched GO category among the up-regulated genes was immune response. Furthermore, genes classified as “unsaturated fatty acid metabolic process” were also significantly enriched among the up-regulated genes. This expression data suggested that HGF/c-Met signaling pathway positively regulates progression of cell cycle and transcription of placenta specific genes, and negatively regulates inflammatory reaction and fatty acids synthesis in the trophoblasts, thereby coordinating many critical cellular processes in the placenta. Freshly harvested mouse placental trophoblast was enriched for CD9 from wild -type and c-Met KO placenta with 2 independent biological replicates
2013-12-31 | E-GEOD-38342 | biostudies-arrayexpress
Project description:Basophils play crucial roles in type 2 immune responses, such as chronic allergic inflammation and protective immunity against parasites. However, the molecular mechanisms underlying the regulation of proinflammatory molecule production by basophils remain unclear. To investigate the role of RNA-binding proteins (RBPs), we first analyzed the gene expression of CCCH zinc finger proteins in antigen/IgE-stimulated basophils and identified that Zfp36, encoding tristetraprolin (TTP), was the most significantly upregulated gene encoding a CCCH zinc finger protein. To explore the functions of TTP in basophils, we generated TTP-knockout (TTP-KO) mice using the CRISPR-Cas9 method and conducted bulk RNA-seq analysis of antigen/IgE-stimulated basophils from wild-type (WT) and TTP-KO mice. TTP-KO basophils exhibited elevated mRNA expression of pro-inflammatory mediators, such as Il4, Il13, Areg, Ccl3, and Cxcl2, compared to WT basophils, suggesting the key role of TTP in the expression of mRNAs encoding proinflammatory mediators. Since TTP is known to regulate mRNA stability in other immune cell types, we evaluated the mRNA stability of WT and TTP-KO basophils under antigen/IgE stimulation using SLAM-seq [thiol (SH)-Linked Alkylation for the Metabolic sequencing of RNA] analysis. SLAM-seq analysis revealed that the mRNA half-lives of proinflammatory molecules, such as Il4, Il13, Areg, Ccl3, and Cxcl2, were prolonged by TTP deficiency, suggesting the importance of TTP in regulating the stability of mRNAs encoding inflammatory molecules in basophils.
2024-11-17 | GSE272531 | GEO
Project description:Tristetraprolin is a vertebrate CCCH tandem zinc finger protein that can bind to and destabilize certain mRNAs containing AU-rich element binding sites. zfs1 is the single gene in the fission yeast, Schizosaccharomyces pombe, that encodes a protein containing the critical features of the tristetraprolin zinc finger domain. zfs1 has been linked to pheromone signal transduction control and to the coordination of mitosis, but no biological function has been ascribed to the zfs1 protein. Through a functional genomics approach we compared transcript levels in wild-type and zfs1-deficient S. pombe strains; those elevated in the zfs1-deficient strain were examined for the presence of potential tristetraprolin-like binding sites. One such potential target transcript was encoded by arz1, a gene encoding a protein of unknown function that contains armadillo repeats. arz1 mRNA decay was inhibited in the zfs1-deficient strain when it was expressed under the control of a thiamine-repressible promoter. Mutations within one AU-rich element present in the arz1 3’-untranslated region protected this transcript from zfs1-promoted decay, whereas mutating another potential binding site had no effect. Binding assays confirmed a direct interaction between zfs1 and arz1 mRNA-based probes; this interaction was eliminated when key residues were mutated in either zfs1 zinc finger. zfs1 and its targets in S. pombe represent a useful model system for studies of zinc finger protein/AU-rich element interactions that result in mRNA decay. Keywords: knockout comparison, steady-state analysis
2007-11-28 | GSE8122 | GEO
Project description:Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins bind to AU-rich regions in the 3'-untranslated regions (UTR) of target mRNAs, leading to their deadenylation and accelerated decay. Family members in S. cerevisiae influence iron metabolism, whereas the family member in S. pombe leads to defects in cell-cell interactions. In the important human fungal pathogen Candida albicans, deep sequencing of transcripts in mutants deficient in the analogous protein, Zfs1p, revealed 156 transcripts whose levels were significantly increased by at least 1.5-fold. Of these, 113 (72%) contained at least a single predicted TTP family member binding site in their 3âUTR. In contrast, 102 transcripts were significantly down-regulated by 1.5-fold or more, and only 5 (5%) of these contained potential binding sites. Sequences of the proteins encoded by the putative Zfs1p targets were highly conserved among other Candida species, while the predicted Zfs1p binding sites in these mRNAs progressively âdisappearedâ with increasing evolutionary distance from the parental species. The C. albicans results support the concept that the biochemical functions of the TTP family members in fungal organisms are highly conserved, yet each species appears to have evolved its own set of transcripts that are regulated by this mechanism. Strains were grown in YPD media to approximately OD600=0.75 and total RNA was harvested from four biological replicates each of WT and 2 independent isolates of the zfs1 deletion.
2015-12-04 | E-GEOD-53073 | biostudies-arrayexpress