Microglia isolated from juvenile offspring of dams with allergic asthma exhibit methylation and transcriptional alterations to autism risk genes
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ABSTRACT:
PROVIDER: PRJNA371477 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5230100.fastq.gz | Fastqsanger.gz | |||
| SRR5232070.fastq.gz | Fastqsanger.gz | |||
| SRR5230101.fastq.gz | Fastqsanger.gz | |||
| SRR5232071.fastq.gz | Fastqsanger.gz | |||
| SRR5230102.fastq.gz | Fastqsanger.gz |
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Project description:Asthma is one of the most common chronic diseases among pregnant women, and symptoms often worsen during pregnancy. Dysregulation in immune responses during pregnancy, such as those that develop with chronic allergic asthma, increase the risk of a having a child with an Autism Spectrum Disorder (ASD). We recently developed a mouse model of maternal allergic asthma (MAA) that induces alterations in behavioral outcomes of the offspring including changes in sociability, repetitive and perseverative behaviors. Pregnancy is also a time when epigenetic changes help a static genome adapt to the maternal environment, and consequently activation of the maternal immune system may alter the regulation of gene expression in the developing fetal brain. Perinatal exposure to maternal asthma alters DNA methylation of immune-related genes in human infants, suggesting that maternal asthma has long-lasting effects on the offspring’s’ immune function. Here we used the genome-wide approaches of whole genome bisulfite sequencing to examine DNA methylation combined with RNA sequencing to examine gene expression in acutely isolated microglia from juvenile MAA offspring. Differential analysis revealed significant alterations in the epigenome of microglia from MAA compared to PBS treated control offspring and identified genes involved in controlling microglial sensitivity to the environment and shaping both synaptic and long-range neuronal connections in the developing brain. Genes with altered methylation and expression in MAA juvenile microglia significantly overlapped with those identified in adult cortex from offspring of a different maternal immune activation (polyIC) autism model and with a curated list of autism risk genes in human, supporting a role for microglia in the pathogenesis of ASD.
2017-12-20 | GSE94568 | GEO
Project description:Asthma is one of the most common chronic diseases among pregnant women, and symptoms often worsen during pregnancy. Dysregulation in immune responses during pregnancy, such as those that develop with chronic allergic asthma, increase the risk of a having a child with an Autism Spectrum Disorder (ASD). We recently developed a mouse model of maternal allergic asthma (MAA) that induces alterations in behavioral outcomes of the offspring including changes in sociability, repetitive and perseverative behaviors. Pregnancy is also a time when epigenetic changes help a static genome adapt to the maternal environment, and consequently activation of the maternal immune system may alter the regulation of gene expression in the developing fetal brain. Perinatal exposure to maternal asthma alters DNA methylation of immune-related genes in human infants, suggesting that maternal asthma has long-lasting effects on the offspring’s’ immune function. Here we used the genome-wide approaches of whole genome bisulfite sequencing to examine DNA methylation combined with RNA sequencing to examine gene expression in acutely isolated microglia from juvenile MAA offspring. Differential analysis revealed significant alterations in the epigenome of microglia from MAA compared to PBS treated control offspring and identified genes involved in controlling microglial sensitivity to the environment and shaping both synaptic and long-range neuronal connections in the developing brain. Genes with altered methylation and expression in MAA juvenile microglia significantly overlapped with those identified in adult cortex from offspring of a different maternal immune activation (polyIC) autism model and with a curated list of autism risk genes in human, supporting a role for microglia in the pathogenesis of ASD.
2017-12-20 | GSE94525 | GEO
Project description:Dysregulation in immune responses during pregnancy increases the risk of a having a child with an autism spectrum disorder (ASD). Asthma is one of the most common chronic diseases among pregnant women, and symptoms often worsen during pregnancy. We recently developed a mouse model of maternal allergic asthma (MAA) that induces changes in sociability, repetitive, and perseverative behaviors in the offspring. Since epigenetic changes help a static genome adapt to the maternal environment, activation of the immune system may epigenetically alter fetal microglia, the brain's resident immune cells. We therefore tested the hypothesis that epigenomic alterations to microglia may be involved in behavioral abnormalities observed in MAA offspring. We used the genome-wide approaches of whole genome bisulfite sequencing to examine DNA methylation and RNA sequencing to examine gene expression in microglia from juvenile MAA offspring. Differentially methylated regions were enriched for immune signaling pathways and important microglial developmental transcription factor binding motifs. Differential expression analysis identified genes involved in controlling microglial sensitivity to the environment and shaping neuronal connections in the developing brain. Differentially expressed genes significantly overlapped genes with altered expression in human ASD cortex, supporting a role for microglia in the pathogenesis of ASD.
| S-EPMC5767155 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-12-20 | GSE94569 | GEO
Project description:Maternal chromium restriction may disturb susceptibility in offspring. Adipose from maternal chromium diet has 1214 CpG sites that exhibit differential DNA methylationregulated compared to control. We performed DNA methylation array analyses of offspring adipose from chromium restriction dams and control diet dams at 32 week (n=3 per group).
2016-09-08 | E-GEOD-82030 | biostudies-arrayexpress
Project description:Obesity is associated with severe, difficult to control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment strategy. Using a mouse model of house dust mite (HDM) induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ); we investigated the effects of obesity and mROS on airway inflammation, remodelling and airway hyperreactivity (AHR). HDM induces airway inflammation, remodelling and hyperreactivity in both lean and obese mice. Obese allergic mice showed increased lung tissue eotaxin levels, airway tissue eosinophilia and AHR when compared to lean allergic mice. MitoQ reduced markers of airway inflammation, remodelling and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obeseHDM mice. mROS regulates cell signalling by protein oxidation of multiple downstream targets: MitoQ reduced HDM-induced cysteine-sulfenylation of several proteins including those involved in the unfolded protein response (UPR). In summary, mROS mediates the development of allergic airway disease and hence MitoQ might be effective for the treatment for asthma, and specific features of obese asthma.
2023-06-02 | PXD029715 | Pride
Project description:Exposure to nanomaterials (NM) during sensitive stages of development may predispose organisms to diseases later in life. However, direct translocation of NM from mother to fetus through the placenta is limited. The present study tests the hypothesis that pulmonary exposure to NM and NM-induced stress, such as inflammation during gestation, can lead to secondary effects in the growing fetus. Time mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Milli Q water) or one of three concentrations (2.75, 13.5 or 67 µg/animal) of carbon black Printex 90 (CB) dispersions on gestational days 7, 10, 15 and 18 to a total final dose of 11, 54 or 268 µg/animal. Male and female newborns were sacrificed on day 2 after birth (PND2, 4 days after the last maternal exposure) and dams were sacrificed after weaning of offspring (26-27 days post-exposure). Histopathology, DNA microarrays, pathway-specific RT-PCR arrays, focussed RT-PCR, and tissue protein analysis were employed to characterize pulmonary response in dams exposed to CB during gestation. Gene expression profiles in newborn livers were interpreted in light of toxic effects of CB to dams indicated by gene expression profiles of dam lungs. Although retention of CB particles was observed in dams from both medium and high dose groups, neutrophil-marked inflammation was significant only in the high dose group dams. Inflammation in dams was accompanied by altered expression of several cytokines and chemokines both at the transcriptional and tissue protein levels. Analysis of newborn livers by DNA microarrays revealed that female offspring were much more sensitive to maternal stress than males. Cellular signalling, inflammation, immune response, cell cycle and lipid metabolism were among the biological pathways affected in female offspring. Males however, responded with subtle changes in genes involved in metabolism. At present, the implications of altered biological pathways in offspring in response to in utero exposure to particles are not well understood. Further investigation will be required to determine if there are long term consequences to offspring in terms of health and responses to environmental stresses.
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Project description:The adult offspring of MHV68 infected dams had a significantly decreased expression of genes linked to dopamine neurons (Th, lmx1b, and foxa1). Deconvolution analysis revealed that the proportion of dopamine neurons in the midbrain was reduced. Pathway analyses indicated mitochondrial dysfunction, with reductions in genes associated with ATP synthesis, mitochondrial respiratory chain, and mitochondrial translation in the offspring of dams infected with MHV68. TIGAR (a negative regulator of mitophagy) and SDHA (mitochondrial complex II subunit) protein levels were increased, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum were increased in these offspring. No such changes were observed in the offspring of dams infected with MCMV.
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2021-04-01 | GSE145505 | GEO
Project description:Exposure to nanomaterials (NM) during sensitive stages of development may predispose organisms to diseases later in life. However, direct translocation of NM from mother to fetus through the placenta is limited. The present study tests the hypothesis that pulmonary exposure to NM and NM-induced stress, such as inflammation during gestation, can lead to secondary effects in the growing fetus. Time mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Milli Q water) or one of three concentrations (2.75, 13.5 or 67 µg/animal) of carbon black Printex 90 (CB) dispersions on gestational days 7, 10, 15 and 18 to a total final dose of 11, 54 or 268 µg/animal. Male and female newborns were sacrificed on day 2 after birth (PND2, 4 days after the last maternal exposure) and dams were sacrificed after weaning of offspring (26-27 days post-exposure). Histopathology, DNA microarrays, pathway-specific RT-PCR arrays, focussed RT-PCR, and tissue protein analysis were employed to characterize pulmonary response in dams exposed to CB during gestation. Gene expression profiles in newborn livers were interpreted in light of toxic effects of CB to dams indicated by gene expression profiles of dam lungs. Although retention of CB particles was observed in dams from both medium and high dose groups, neutrophil-marked inflammation was significant only in the high dose group dams. Inflammation in dams was accompanied by altered expression of several cytokines and chemokines both at the transcriptional and tissue protein levels. Analysis of newborn livers by DNA microarrays revealed that female offspring were much more sensitive to maternal stress than males. Cellular signalling, inflammation, immune response, cell cycle and lipid metabolism were among the biological pathways affected in female offspring. Males however, responded with subtle changes in genes involved in metabolism. At present, the implications of altered biological pathways in offspring in response to in utero exposure to particles are not well understood. Further investigation will be required to determine if there are long term consequences to offspring in terms of health and responses to environmental stresses.
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