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Integrative epigenomic analyses of early-life hypothalamic response to augmented maternal care [miRNA]

ABSTRACT: The quality of maternal care in early-life plays a crucial role in mammalian neurodevelopment. Augmented maternal care (AMC) is a well-established rodent model of enhanced neonatal care. Rats that have undergone AMC have improved stress resilience and cognition compared with rats that have experienced normal levels of maternal care or adverse neonatal stress. However, the epigenomic basis of long-lived responses to AMC has not been previously explored. Thus, we employed whole-genome bisulfite sequencing (WGBS), RNA-sequencing (RNA-seq), and a multiplex microRNA (miRNA) assay to assess DNA cytosine methylation, gene expression, and miRNA expression, respectively. The integrated results identify a suite of 20 prioritized candidates impacted by AMC. Overall, these results identified AMC-induced regulatory differences in genes related to neurotransmission, neurodevelopment, protein synthesis, and oxidative phosphorylation in addition to the expected stress response genes. Together, these unbiased results represent a key progression in understanding the complex mechanisms underlying the early-life mechanisms for AMC programming stress resiliency.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE99281 | GEO | 2019/04/21

REPOSITORIES: GEO

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Integrative epigenomic analyses of early-life hypothalamic response to augmented maternal care [RNA-seq]

Project description:The quality of maternal care in early-life plays a crucial role in mammalian neurodevelopment. Augmented maternal care (AMC) is a well-established rodent model of enhanced neonatal care. Rats that have undergone AMC have improved stress resilience and cognition compared with rats that have experienced normal levels of maternal care or adverse neonatal stress. However, the epigenomic basis of long-lived responses to AMC has not been previously explored. Thus, we employed whole-genome bisulfite sequencing (WGBS), RNA-sequencing (RNA-seq), and a multiplex microRNA (miRNA) assay to assess DNA cytosine methylation, gene expression, and miRNA expression, respectively. The integrated results identify a suite of 20 prioritized candidates impacted by AMC. Overall, these results identified AMC-induced regulatory differences in genes related to neurotransmission, neurodevelopment, protein synthesis, and oxidative phosphorylation in addition to the expected stress response genes. Together, these unbiased results represent a key progression in understanding the complex mechanisms underlying the early-life mechanisms for AMC programming stress resiliency.

2019-04-21 | GSE99278 | GEO

Integrative epigenomic analyses of early-life hypothalamic response to augmented maternal care [BiSulfite-seq]

2019-04-21 | GSE99272 | GEO

Broad epigenetic signature of maternal care in the brain of adult rats (DNA methylation and H3K9 acetylation profiles)

2011-03-09 | GSE20714 | GEO

Broad epigenetic signature of maternal care in the brain of adult rats (expression)

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Broad epigenetic signature of maternal care in the brain of adult rats (DNA methylation and H3K9 acetylation profiles)

Project description:Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, epigenetic changes at a single gene promoter are unlikely to account for the range of responses to the early life environment and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. Here we show that natural variations in maternal care are associated with coordinate changes in DNA methylation, chromatin, and gene expression spanning over a hundred kilobase pairs in the hippocampus of adult rats. The offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends and higher transcriptional activity across many genes, suggesting that a broad epigenetic regulation of gene expression may form part of a coordinated response to early maternal care. We obtained hippocampal samples from adult offspring of rat mothers that differed in the frequency of pup licking/grooming in the first week of life. Using custom-designed microarrays with probes tiling the 7 million base pair region of rat chromosome 18 centered at the NR3C1 gene at 100 bp spacing, we obtained DNA methylation and H3K9 acetylation profiles by ChIP-on-chip. Each profile was generated in triplicate, each type of profile from 3 high frequency and 3 low frequency mothers.

2011-03-09 | E-GEOD-20714 | biostudies-arrayexpress

Broad epigenetic signature of maternal care in the brain of adult rats (expression)

Project description:Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, epigenetic changes at a single gene promoter are unlikely to account for the range of responses to the early life environment and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. Here we show that natural variations in maternal care are associated with coordinate changes in DNA methylation, chromatin, and gene expression spanning over a hundred kilobase pairs in the hippocampus of adult rats. The offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends and higher transcriptional activity across many genes, suggesting that a broad epigenetic regulation of gene expression may form part of a coordinated response to early maternal care. We obtained hippocampal samples from adult offspring of rat mothers that differed in the frequency of pup licking/grooming in the first week of life, 4 from high frequency and 4 from low frequency mothers. Using custom-designed microarrays with probes tiling the 7 million base pair region of rat chromosome 18 centered at the NR3C1 gene at 100 bp spacing, we obtained transcription profiles by hybridizing cDNA to microarrays. Each profile was generated in duplicate.

2011-03-09 | E-GEOD-20717 | biostudies-arrayexpress

Integrative epigenomic analyses of early-life hypothalamic response to augmented maternal care

Project description:Integrative epigenomic analyses of early-life hypothalamic response to augmented maternal care

| PRJNA387922 | ENA

Broad epigenetic signature of maternal care in the brain of adult rats

Project description:This SuperSeries is composed of the following subset Series: GSE20714: Broad epigenetic signature of maternal care in the brain of adult rats (DNA methylation and H3K9 acetylation profiles) GSE20717: Broad epigenetic signature of maternal care in the brain of adult rats (expression) Refer to individual Series

2011-03-09 | E-GEOD-20840 | biostudies-arrayexpress

Gene analysis of the neonatal rat lung exposed to STZ-induced maternal diabetes

Project description:Maternal diabetes is associated with a wide range of fetal and neonatal adverse effects including pulmonary disturbances. To investigate the effects of maternal diabetes on neonatal lung gene expression profile, we performed microarray analysis on the lungs of 14-day-old rats born to diabetic dam. Keywords: disease state analysis Four neonatal lungs exposed to maternal diabetes and four control lungs were analyzed.

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Project description:The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the developmental gene expression in the hippocampus and amygdala. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus). All samples were generated from Sprague-Dawley male rats selectively bred for high novelty response (HRs), low novelty response (LRs) or LRs that were crossfostered to either a LR dame or HR dame.

2016-10-19 | GSE88874 | GEO

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