Ontology highlight
ABSTRACT:
PROVIDER: PRJNA673393 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12952490.fastq.gz | Fastqsanger.gz | |||
| SRR12952491.fastq.gz | Fastqsanger.gz | |||
| SRR12952492.fastq.gz | Fastqsanger.gz | |||
| SRR12952493.fastq.gz | Fastqsanger.gz | |||
| SRR12952494.fastq.gz | Fastqsanger.gz |
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Project description:Diabetes mellitus in early pregnancy is a non–genetic maternal risk factor for neural tube defects, which are associated with dysregulated gene expression and disruption of cellular behaviors. However, the key molecules linking high glucose metabolism to gene dysregulation remain unclear. Here, we report elevation of ATP citrate lyase (ACL), a metabolic enzyme of the glucose–related tricarboxylic acid cycle in brains of DM–induced mouse embryos with neural tube defects. Consistent with high glucose exposure, manipulation of ACL expression controlled the levels of acetyl-CoA and subsequent lysine 27 acetylation of histone H3 (H3K27ac). Inhibition of ACL activity significantly ameliorated diabetes mellitus–induced exencephaly in mouse embryos. Combinational analysis of H3K27ac ChIP-seq and RNA-seq data revealed a genome–wide synergistic dysregulation of 566 genes, among which the most highly upregulated gene was Txnip, which encodes a thioredoxin–interacting protein. Manipulation of ACL expression disrupted the levels of TXNIP protein, subsequent phosphorylation of apoptosis signal–regulating kinase 1 (ASK1) and neuroepithelial apoptosis. Such pathogenic pathway involving high glucose–induced ACL–H3K27ac, increased–TXNIP upregulation and excessive apoptosis was validated in human embryonic brain tissue affected by neural tube defects. Our study uncovers an intermediary role of ACL in linking high glucose metabolism to epigenetic alterations and neural tube defect formation.
2023-08-31 | GSE239962 | GEO
Project description:Diabetes mellitus in early pregnancy is a non–genetic maternal risk factor for neural tube defects, which are associated with dysregulated gene expression and disruption of cellular behaviors. However, the key molecules linking high glucose metabolism to gene dysregulation remain unclear. Here, we report elevation of ATP citrate lyase (ACL), a metabolic enzyme of the glucose–related tricarboxylic acid cycle in brains of DM–induced mouse embryos with neural tube defects. Consistent with high glucose exposure, manipulation of ACL expression controlled the levels of acetyl-CoA and subsequent lysine 27 acetylation of histone H3 (H3K27ac). Inhibition of ACL activity significantly ameliorated diabetes mellitus–induced exencephaly in mouse embryos. Combinational analysis of H3K27ac ChIP-seq and RNA-seq data revealed a genome–wide synergistic dysregulation of 566 genes, among which the most highly upregulated gene was Txnip, which encodes a thioredoxin–interacting protein. Manipulation of ACL expression disrupted the levels of TXNIP protein, subsequent phosphorylation of apoptosis signal–regulating kinase 1 (ASK1) and neuroepithelial apoptosis. Such pathogenic pathway involving high glucose–induced ACL–H3K27ac, increased–TXNIP upregulation and excessive apoptosis was validated in human embryonic brain tissue affected by neural tube defects. Our study uncovers an intermediary role of ACL in linking high glucose metabolism to epigenetic alterations and neural tube defect formation.
2023-08-31 | GSE239961 | GEO
Project description:Exposure to ionizing radiation around the time of neural tube closure results in a number of developmental defects, including neural tube defects (e.g. exencephaly, cleft palate) and eye defects (e.g. microphtalmos, anaphtalmos). These defects result from perturbed neural tube closure and development of the presumptive eye. In order to better understand the underlying molecular mechanisms, gene expression profiling was performed in heads of mouse embryos at embryonic day 9, after they had been irradiated at embryonic day 7.5 with 1 Gy of X-rays. Non-irradiated mice served as controls for differential gene expression.
2019-09-02 | E-MTAB-7532 | biostudies-arrayexpress
Project description:Background The vitamin A derivative, retinoic acid (RA), is a potent teratogenic agent that induces a variety of congenital abnormalities including neural tube defects. The embryopathology of RA has been extensively investigated and retinol receptors play important roles during organogenesis, development and neural tube closure. Still, the mechanisms by which RA influences these processes are not completely understood. Methods We used a custom-made mouse genome 32K oligonucleotide microarray to determine the gene expression profiles of mouse embryo spinal cord samples that had been exposed to vehicle or RA. Then, we performed a GSEA (gene set enrichment analysis) on the gene expression data by searching MSigDB (v2.5) c2 gene sets (canonical pathways) and c5 gene sets (curated GO terms), with set size restraints on the range to avoid over-narrow or over-broad categories. Results Using microarray technology, the present study identifies 85 genes in the spinal cord that exhibit at least a 1.5-fold change between control samples and samples with spina bifida aperta. A gene set enrichment analysis showed that maternal exposure to RA induced spinal bifida that were associated with altered expression of genes involved in pro- or anti-apoptosis, cell proliferation, migration, cytoskeleton components, and cell or focal adhesion, indicating that defective functions of these cell components and biological processes preceded the abnormal development of neural tube. Conclusions Maternal exposure to RA induced spinal bifida that were associated with altered expression of genes involved in pro- or anti-apoptosis, cell proliferation, migration, cytoskeleton components, and cell or focal adhesion. As shown in previous reports, defective functions of these cell components and biological processes preceded the abnormal development of the neural tube. Our study will help the understanding of the etiology and pathology of spinal bifida. However, it should be noted that the changes in gene expression induced by RA exposure may not be an effect on events other than neural tube closure; further study is required to fully understand the molecular mechanisms and consequence of neural tube defects in embryos exposed to RA. Our study provides a global analysis of gene expression patterns in spina bifida and will help the understanding of the etiology and pathology of neural tube defects. We assessed the changes in gene expression that coincide with spina bifida in RA-treated mouse fetuses. After generating an independent list of regulated genes, we analyzed samples by gene set enrichment analysis to expand our results. A pool of spinal cord tissue from spina bifida fetuses whose mothers were exposed to RA was compared to a pool of spinal cord tissue from fetuses whose mothers were exposed to olive oil vehicle. Three replicates each.
2011-05-10 | E-GEOD-28834 | biostudies-arrayexpress
Project description:Background The vitamin A derivative, retinoic acid (RA), is a potent teratogenic agent that induces a variety of congenital abnormalities including neural tube defects. The embryopathology of RA has been extensively investigated and retinol receptors play important roles during organogenesis, development and neural tube closure. Still, the mechanisms by which RA influences these processes are not completely understood. Methods We used a custom-made mouse genome 32K oligonucleotide microarray to determine the gene expression profiles of mouse embryo spinal cord samples that had been exposed to vehicle or RA. Then, we performed a GSEA (gene set enrichment analysis) on the gene expression data by searching MSigDB (v2.5) c2 gene sets (canonical pathways) and c5 gene sets (curated GO terms), with set size restraints on the range to avoid over-narrow or over-broad categories. Results Using microarray technology, the present study identifies 85 genes in the spinal cord that exhibit at least a 1.5-fold change between control samples and samples with spina bifida aperta. A gene set enrichment analysis showed that maternal exposure to RA induced spinal bifida that were associated with altered expression of genes involved in pro- or anti-apoptosis, cell proliferation, migration, cytoskeleton components, and cell or focal adhesion, indicating that defective functions of these cell components and biological processes preceded the abnormal development of neural tube. Conclusions Maternal exposure to RA induced spinal bifida that were associated with altered expression of genes involved in pro- or anti-apoptosis, cell proliferation, migration, cytoskeleton components, and cell or focal adhesion. As shown in previous reports, defective functions of these cell components and biological processes preceded the abnormal development of the neural tube. Our study will help the understanding of the etiology and pathology of spinal bifida. However, it should be noted that the changes in gene expression induced by RA exposure may not be an effect on events other than neural tube closure; further study is required to fully understand the molecular mechanisms and consequence of neural tube defects in embryos exposed to RA. Our study provides a global analysis of gene expression patterns in spina bifida and will help the understanding of the etiology and pathology of neural tube defects.
2011-05-10 | GSE28834 | GEO
Project description:Folic acid supplements prior to and during gestation are recommended and necessary to prevent neural tube defects in developing embryos. But there are also studies suggesting possible adverse effects of high-dose folic acid supplementation. Here, we address whether maternal dietary folic acid supplementation at 40 mg/kg chow (FD), restricted to a period prior to conception, affects gene expression in the offspring generation.
2017-06-08 | GSE80587 | GEO
Project description:Maternal diabetes is a teratogen that can lead to neural tube closure defects in the offspring. We therefore sought to compare gene expression profiles at the site of neural tube closure between stage-matched embryos from normal dams, and embryos from diabetic dams. Neurulation-stage mouse embryos at 8.5 days of gestation were used to prepare neural tissue at the anterior aspect of neural tube closure site 1. Tissue was procured from the open neural tube immediately anterior of the closure site, and from the closed neural tube immediately posterior to the closure site by laser microdissection. For each sample, 10 sections were pooled, total RNA was extracted, and 7 ng of total RNA were used for expression profiling by Tag sequencing using an Applied Biosystems SolidSAGE kit for library construction, and an AB SOLiD 5500 XL instrument for sequencing. Sequence reads were mapped to RefSeq RNA, and count data per gene were obtained using a modified version of the Applied Biosystems SOLiDâ?¢ SAGEâ?¢ Analysis Software. diabetic dam - closed neural tube // diabetic dam - open neural tube // normal dam - closed neural tube // normal dam - open neural tube
2016-10-24 | E-GEOD-41876 | biostudies-arrayexpress
Project description:To better understand the role of Geminin during germ layer specification, we bred floxed Geminin mice to Mox2-Cre mice. Mutants (fl/fl; cre/o) had spinal neural tube defects with complete penetrance. We obtained neural tube and paraxial tissue by laser capture microdissection and analyzed total RNA by microarray. Spinal neural tube and paraxial tissue were obtained separately by laser capture microdissection from wild-type and mutant E10.5 embryos. There were 2 replicates of each sample.
2014-09-30 | E-GEOD-42052 | biostudies-arrayexpress
Project description:In order to more thoroughly investigate the mechanism of arsenate-induced NTDs we designed experiment in which highly sensitive Folr2 nullizygous mice were treated i.p. with teratogenic dose of sodium arsenate just at the beginning of the neural tube formation process. This specific knockout mouse and arsenic exposure conditions were chosen as they warranted high incidence of exencephaly in exposed embryos. We investigated the gene expression changes induced by arsenic in the anterior part of neural tube in order to discover patterns that might shed light on the mechanism of arsenic’s teratogenicity. Keywords: toxic response
2005-12-30 | GSE3412 | GEO
Project description:The antiepileptic drug valproic acid (vpa) is known teratogen giving neural tube defects (ntd:s). Administration of vpa to female NMRI on gestation day 8 induces a high incidence of ntd. In this study we investigate the time dependent gene expression changes induced in the embryo 1.5, 3 respectively 6 hr after maternal sodium valproate treatment.
2008-03-28 | E-MEXP-1062 | biostudies-arrayexpress