Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE189945 | GEO | 2021/12/07
REPOSITORIES: GEO
Similar Datasets
Project description:Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and occurs in genomic regions enriched for heritability of body mass index in humans. Our results offer a potential explanation for both the limited ontogenic windows for and sex differences in sensitivity to developmental programming of obesity and provide a rich resource for epigenetic analyses of developmental programming of energy balance.
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Project description:Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index
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Project description:To better understand the epigenetic mechanism underlying pubertal onset, the hypothalamic genome-wide chromatin accessibility patterns in mouse arcuate nucleus at early and late pubertal stages were explored. Female mice have been widely used in multiple studies on pubertal development as they present the similar molecular behaviors in HPG axis and stable cycles of menstrual calendar like human. Hypothalamic ARC underwent a huge epigenetic and genetic reprogramming to adapt to the response and feedback on sexual hormones during the stages of early pubertal (2-5-week of age) and late puberty (5-8-week of age) . We harvested 4- and 8-week hypothalamic ARC and employed ATAC-seq on a genome-wide scale. Combined with previous RRBS, RRHP and RNA-seq, the connections between DNA (hydroxyl)methylation in retroelements and gene expression were studied, emphasizing the importance of epigenetic alterations in regulating transcription in puberty onset.
2021-04-02 | E-MTAB-10263 | biostudies-arrayexpress
Project description:To better understand the epigenetic mechanism underlying pubertal onset, the hypothalamic genome-wide DNA methylation and hydroxymethylation patterns as well as the transcription profiles in mouse arcuate nucleus at early and late pubertal stages were explored. Female mice have been widely used in multiple studies on pubertal development as they present the similar molecular behaviors in HPG axis and stable cycles of menstrual calendar like human. Hypothalamic ARC underwent a huge epigenetic and genetic reprogramming to adapt to the response and feedback on sexual hormones during the stages of early pubertal (2-5-week of age) and late puberty (5-8-week of age) . We harvested 4- and 8-week hypothalamic ARC and employed RNA-seq, reduced representation bisulfite sequencing (RRBS) and hydroxymethylation profiling (RRHP) on a genome-wide scale. We identified a large number of differential expressed genes (DEGs) and differential 5(h)mC signals across the whole genome. We discovered novel connections between DNA (hydroxyl)methylated modification and gene expression, emphasizing the importance of epigenetic alterations in regulating transcription in puberty onset.
2020-08-21 | E-MTAB-9421 | biostudies-arrayexpress
Project description:To better understand the epigenetic mechanism underlying pubertal onset, the hypothalamic genome-wide DNA methylation and hydroxymethylation patterns as well as the transcription profiles in mouse arcuate nucleus at early and late pubertal stages were explored. Female mice have been widely used in multiple studies on pubertal development as they present the similar molecular behaviors in HPG axis and stable cycles of menstrual calendar like human. Hypothalamic ARC underwent a huge epigenetic and genetic reprogramming to adapt to the response and feedback on sexual hormones during the stages of early pubertal (2-5-week of age) and late puberty (5-8-week of age) . We harvested 4- and 8-week hypothalamic ARC and employed RNA-seq, reduced representation bisulfite sequencing (RRBS) and hydroxymethylation profiling (RRHP) on a genome-wide scale. We identified a large number of differential expressed genes (DEGs) and differential 5(h)mC signals across the whole genome. We discovered novel connections between DNA (hydroxyl)methylated modification and gene expression, emphasizing the importance of epigenetic alterations in regulating transcription in puberty onset.
2020-08-20 | E-MTAB-9420 | biostudies-arrayexpress
Project description:We performed ATAC-seq on iPSC-derived hypothalamic arcuate-like neuron cells to identify putative regulatory elements. All samples were derived from the same individual and from the same differentiation/cell line but ATAC-seq was performed in 3 separate experiments (3 technical replicates).
2021-04-01 | E-MTAB-10257 | biostudies-arrayexpress
Project description:Chromatin accessibility in mouse hypothalamic arcuate nucleus in puberty onset
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Project description:Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes. Disruption of neuronatin results in an unusual phenotype of a bimodal body weight.In order to understand at the molecular level how the Nnat deficiency could contribute to the hypervariable phenotypes seen, we performed RNA sequencing from laser-capture micro dissected paraventricular nucleus (PVN) and arcuate nucleus (ARC) and compared the transcriptome between Nnat+/-p mice and their Nnat+/+ littermates in different feeding conditions. We performed an analysis of three subgroups: Nnat+/+ (all non-obese), Nnat+/-p non-obese, and Nnat+/-p obese mice and combined two approaches to identify differences in hypothalamic gene expression between subgroups
2021-09-03 | GSE171155 | GEO
Project description:Over recent decades, research has established the hypothalamus, particularly the arcuate nucleus, as a central hub for the homeostatic control of energy balance. The hypothalamic arcuate nucleus is a pivotal regulator of energy balance, containing anorexic proopiomelanocortin (POMC) neurons and orexigenic agouti-related peptide (AgRP) neurons, which exert opposing effects on energy homeostasis. However, the molecular identity of “non-AgRP, non-POMC” neurons remains unclear. We identified a distinct neuronal subtype characterized by the absence of Agrp and Pomc expressions, while exhibiting robust Crabp1 expression.
2024-12-10 | GSE276414 | GEO
Project description:The electroacupuncture-induced analgesic effect has been used widely to alleviate diverse pains. However, significant individual variations in analgesic effect of EA for both experiments and clinics were reported. According to the sensitivity of the analgesic response to EA stimulation, the subjects could be categorized into high responders (HR) and non responders (NR). However, the molecular mechanism of individual variability in the analgesic response to acupuncture stimulation is still uncertain. This study aims to investigate the potential gene expression in arcuate nucleus induced by 2Hz/100Hz electroacupuncture in HR and NR rats. Rats were given 2Hz or 100Hz electroacupuncture for 30 min and using cDNA microarrays to compare different gene expression in arcuate nucleus. Rats were exposed to different frequencies (2Hz or 100Hz) electroacupuncture stimulation for 30 min and nociceptive testing and returned to home cages for 1 hour before sacrificed. According to the sensitivity of the analgesic response to 2Hz or 100Hz EA stimulation, the rats divided into four groups: 2Hz-HR group, 2Hz-NR group, 100Hz-HR group and 100Hz-NR group. Subsequently analyzed their dorsal horn transcript profile using cDNA microarrays, the rats were without receiving electroacupuncture as control. The tissue of arcuate nucleus (Arc) of three rats was selected for transcript analysis in each group. The three control rats were mixed and labeled with cy5, each rat of experiment groups was labeled with cy3.
2011-07-07 | E-GEOD-30365 | biostudies-arrayexpress