Project description:<p>Maternal folic acid intake is crucial for the development of the offspring's nervous system, and folic acid metabolism disorders during pregnancy lead to neural tube defects (NTDs) in the fetus. Folic acid and vitamins biosynthesis is a major biochemical feature of gut microbiota. The complex and diverse microbial ecosystem residing within maternal host contributes critically to these intergenerational impacts. However, the mechanisms still require further investigation. In this study, we found that the low folate diets combined MTX-induced changed the structure/composition of the gut microbiota and substantially altered the fecal metabolic phenotype of pregnant mice, including central carbon metabolism in cancer and vitamin digestion & absorption. We demonstrated that the correlation betweent gut microbiota of pregnant mice and the brain metabolic profiles of NTDs fetal mice. According to our data, the Lactobacillales and Bifidobacteriales abundances in pregnant mice gut were positively correlated with the abundances of lipid metabolites in fetal mice brain. The abundances of Enterobacterales and Clostridiales were negatively correlated with those lipid metabolites. Interestingly, the abundance of Inosine, Uridine, L-Carnitine and Glycerophosphocholine were down-regulated synchronously in pregnant feces and NTDs fetal mice brain. This was probably the intergenerational microbial-metabolism biomarkers of NTDs. Our study provides evidence for how perinatal microecological factors shape fetal neural tube development.</p><p><br></p><p><strong>Feces metabolomics</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS4893' rel='noopener noreferrer' target='_blank'><strong>MTBLS4893</strong></a>.</p><p><strong>Brain tissue metabolomics</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4894' rel='noopener noreferrer' target='_blank'><strong>MTBLS4894</strong></a>.</p>
Project description:To investigate the associated with abnormal DNA demethylation and neural tube defects (NTDs) with folate deficiency, we etablished mouse embryonic stem cells (mESCs) Sv/129 in folate-deficiency-treated.
Project description:To investigate the associated with abnormal DNA demethylation and neural tube defects (NTDs) with folate deficiency, we etablished mouse embryonic stem cells (mESCs) Sv/129 in folate-deficiency-treated.
Project description:To investigate the associated with DNA demethylation and neural tube defects (NTDs) with folate deficiency, we etablished mouse embryonic stem cells (mESCs) Sv/129 in folate-deficiency-treated.
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
Project description:At an incidence of approximately 1/1000 births, neural tube defects (NTDs) comprise one of the most common and devastating congenital disorders. In an attempt to enhance and expand our understanding of neural tube closure, we undertook a high-throughput gene expression analysis of the neural tube as it was forming in the mouse embryo. Open and closed sections of the developing neural tube were micro-dissected from mouse embryos, and hybridized to Affymetrix mouse expression arrays. Clustering of genes differentially regulated in open and closed sections of the developing neural tube highlighted molecular processes previously recognized to be involved in neural tube closure and neurogenesis. Analysis of the genes in these categories identified potential candidates underlying neural tube closure. In addition, we identified approximately 25 novel genes, of unknown function, that were significantly up-regulated in the closed neural tube. Based on their expression patterns in the developing neural tube, five novel genes are proposed as interesting candidates for involvement in neurogenesis. The high-throughput expression analysis of the neural tube as it forms allows for better characterization of pathways involved in neural tube closure and neurogenesis, and hopefully will strengthen the foundation for further research along the pathways dictating neural tube development.
Project description:Background: Neural tube defects (NTDs) are congenital malformations that occur when the neural tube fails to close properly during early embryonic development. However, the identity of affected celltypes and pathogenic mechanisms remain unclear due to the lack of clinical samples. Method: We utilized single-nucleus RNA sequencing to analyze 37,064 neural tube cells from NTDs and normal abortus at 14 and 15 gestational weeks. Multiplexed immunofluorescence staining was performed to further validate some phenotypes. Results: Firstly, we revealed that the most affected celltypes are excitatory neurons, inhibitory neurons, and astrocytes. We further elucidated that the main subtypes mediating abnormal development in NTDs is IGF2high subtypes in inhibitory neurons and MEG3high subtypes in astrocytes. Importantly, our findings highlighted IGF2 as a pivotal gene for abnormal development and abnormal cell-cell communications in NTDs. Conclusions: In summary, this study presents the first single-cell atlas of NTDs and provides new insights for further research into the underlying mechanisms of NTDs.