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| Status |
Public on Dec 20, 2017 |
| Title |
Microglia isolated from juvenile offspring of dams with allergic asthma exhibit methylation and transcriptional alterations to autism risk genes [WGBS] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Whole genome bisulfte sequencing was performed on acutely isolated microglia from female C57BL6/J mice whose mother's had either received maternal immune activation (gestational day9,12, and 17) or PBS treatment. 4 MAA and 4 PBS biological replicates
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| Contributor(s) |
Ciernia AV, LaSalle J |
| Citation(s) |
29134693 |
| |
| Submission date |
Feb 06, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Annie Vogel Ciernia |
| E-mail(s) |
annie.ciernia@ubc.ca
|
| Phone |
6048270752
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| Organization name |
University of British Columbia
|
| Street address |
2215 Wesbrook Mall room 4550, Centre for Brain Health
|
| City |
Vancouver |
| State/province |
British Columbia |
| ZIP/Postal code |
V6T 2A1 |
| Country |
Canada |
| |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE94569 |
Microglia isolated from juvenile offspring of dams with allergic asthma exhibit methylation and transcriptional alterations to autism risk genes |
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| Relations |
| BioProject |
PRJNA371520 |
| SRA |
SRP099007 |
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