Fetal origin of sex-bias brain aging [RNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE215138 | GEO | 2022/10/12
REPOSITORIES: GEO
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Project description:DNA methylation plays crucial roles during fetal development as well as aging. Whether the aging of the brain is programmed at the fetal stage remains untested. To test this hypothesis, mouse epigenetic clock (epiclock) was profiled in fetal (gestation day 15), postnatal (day 5), and aging (week 70) brain of male and female C57BL/6J inbred mice. Data analysis showed that on week 70, the female brain was epigenetically younger than the male brain. Predictive modeling by neural network identified specific methylations in the brain at the developing stages that were predictive of epigenetic state of the brain during aging. Transcriptomic analysis showed coordinated changes in the expression of epiclock genes in the fetal brain relative to the placenta. Whole-genome bisulfite sequencing identified sites that were methylated both in the placenta and fetal brain in a sex-specific manner. Epiclock genes and genes associated with specific signaling pathways, primarily the gonadotropin-releasing hormone receptor (GnRHR) pathway, were associated with the sex-bias methylations in the placenta as well as the fetal brain. Transcriptional crosstalk among the epiclock and GnRHR pathway genes was evident in the placenta that was maintained in the brain during development as well as aging. Collectively, these findings suggest that sex differences in the aging of the brain are of fetal origin and epigenetically linked to the placenta.
2022-08-22 | GSE157553 | GEO
Project description:Fetal origin of sex-bias brain aging
| PRJNA661735 | ENA
Project description:Fetal origin of sex-bias brain aging [RNA-seq]
| PRJNA888983 | ENA
Project description:An allele of a gene can be epigenetically regulated to show a parent-of-origin biasedexpression pattern, a phenomenon referring to as genomic imprinting. Genomic imprinting ishighly tissue-specific, and mammalian brains are hotspots for this effect. Social behaviourdefects in human and various behavioural changes in mouse, had been linked toinappropriate imprinting, but little is known about how and why such effects occur.The olfactory system in the brain is the essential sensory circuitry that mediates rodent innatebehaviour. Meanwhile, monoallelic expression, a related process, is used extensively inchemosensory neurons to regulate olfactory and vomeronasal receptor choice. We have datashowing receptor gene choice is not a random process, which implies allele choice may bebiased also. The olfactory system is therefore a promising target for detecting allelicimbalance, or even novel imprinting genes, by high-resolution RNA-sequencing followed byallelic-specific transcriptomic mapping.This project is designed to detect parent-of-origin and strain-of-origin allelic expression bias inneurons from a key olfactory tissues in rodents: vomernasal organ (VNO) . RNA from reciprocally crossed F1 hybrid mice (S-cross and M-cross) from two distinct inbred strains (C57BL/6J and CAST) have been extracted respectively. After sequencing,expression levels from each allele will be distinguished by incorporating SNP and indeldifferences to the strain-specific reference genomes. Analysis will be carried out incollaboration with Gary Churchill's team at the Jackson Laboratory (who have developed amethod of analysing RNAseq data from CAST x C57BL/6J F1s).Genes with strong, reproducible allelic imbalances will be followed up to assess the functional consequences.
2014-12-09 | E-ERAD-318 | biostudies-arrayexpress
Project description:An allele of a gene can be epigenetically regulated to show a parent-of-origin biasedexpression pattern, a phenomenon referring to as genomic imprinting. Genomic imprinting ishighly tissue-specific, and mammalian brains are hotspots for this effect. Social behaviourdefects in human and various behavioural changes in mouse, had been linked toinappropriate imprinting, but little is known about how and why such effects occur.The olfactory system in the brain is the essential sensory circuitry that mediates rodent innatebehaviour. Meanwhile, monoallelic expression, a related process, is used extensively inchemosensory neurons to regulate olfactory and vomeronasal receptor choice. We have datashowing receptor gene choice is not a random process, which implies allele choice may bebiased also. The olfactory system is therefore a promising target for detecting allelicimbalance, or even novel imprinting genes, by high-resolution RNA-sequencing followed byallelic-specific transcriptomic mapping.This project is designed to detect parent-of-origin and strain-of-origin allelic expression bias inneurons from two olfactory tissues: main olfactory epithelium (MOE) and olfaction bulb (OB). RNA from reciprocally crossed F1 hybrid mice (S-cross and M-cross) from two distinct inbred strains (C57BL/6J and CAST) have been extracted respectively (two crosses, two tissue types). After sequencing,expression levels from each allele will be distinguished by incorporating SNP and indeldifferences to the strain-specific reference genomes. Analysis will be carried out incollaboration with Gary Churchill's team at the Jackson Laboratory (who have developed amethod of analysing RNAseq data from CAST x C57BL/6J F1s).Genes with strong, reproducible allelic imbalances will be followed up to assess the functional consequences.
2014-05-27 | E-ERAD-239 | biostudies-arrayexpress
Project description:The objective of the present study is to investigate gene regulation in developing fetal brain in congenic or inbred mice strains that differ in longevity. Gene expression and alternative splice variants were analyzed in a genome-wide manner in the fetal brain of C57BL/6J mice (long-lived), and compared to that of a congenic strain (short-lived) or an inbred strain AKR/J (short-lived) on days 12, 15 and 17 of gestation. The analysis showed a contrasting gene expression pattern during fetal brain development in these mice. Genes related to brain development, aging and spliceosome were significantly differentially regulated in the fetal brain of the short-lived mice when brain developed from d15 to d17. A significantly reduced number of splice variants were observed on d15 compared to d12 or d17 but in a strain-dependent manner.
2024-06-05 | GSE252079 | GEO
Project description:The circadian clock is an evolutionarily conserved mechanism that drives rhythmic expression of downstream genes. The core circadian clock drives the expression of clock-controlled genes either directly or indirectly, which in turn play critical roles in carrying out many rhythmic physiological processes. Nevertheless, the molecular mechanisms by which clock output genes orchestrate rhythmic signals from the brain to peripheral tissues are largely unknown. Here we explored the role of one rhythmic gene, Achilles, in regulating the rhythmic transcriptome in fly heads. Achilles is a clock-controlled gene in Drosophila that encodes a putative RNA-binding protein. Achilles expression is not detectable in core clock neurons using in-situ hybridization, although its expression is found in neurons throughout the fly brain. Together, these observations argue against a role for Achilles in regulating the core clock. To assess its impact on circadian mRNA rhythms, we performed RNA sequencing (RNAseq) to compare the rhythmic transcriptomes of control flies and those with diminished Achilles expression in all neurons. Consistent with previous observations, we observe dramatic upregulation of immune response genes upon knock-down of Achilles. Furthermore, a subset of circadian mRNAs lose their rhythmicity in Achilles knock-down flies, suggesting that a subset of the rhythmic transcriptome is regulated either directly or indirectly by Achilles. These Achilles-mediated rhythms include many genes involved in immune function and neuronal signaling such as Prosap, Nemy and Jhl-21. Comparison of RNAseq data from control flies reveal that only 42.7% of clock-controlled genes in the fly brain are rhythmic in both males and females. As mRNA rhythms of core clock genes are largely invariant between the sexes, this observation suggests that sex-specific mechanisms are an important, and heretofore under-appreciated, regulator of the rhythmic transcriptome.
2018-12-31 | GSE120100 | GEO
Project description:Gender differences in the prevalence of psychiatric disorders are well documented in epidemiological studies. Exposure to stress during gestation impacts differentially between females and males. Environmental or biological factors can alter DNA methylation and affect the development of neurodevelopmental diseases. In this study, we explored gender-specific DNA methylation in regarding their potential connection to psychiatric outcomes. We assessed the methylation of cord blood of 39 females and 32 males born at term and with appropriate weight at birth. Mothers between 18 and 48 years of age (median: 28 years) were interviewed to gather information about environmental factors (gestational exposure) that can potentially interfere with the methylation profiles in the newborns. Bisulphite converted DNA was hybridized to Illumina HumanMethylation450 BeadChips. After exclusion of XYS probes, there were 2,332 differentially methylated CpG sites (DMS) between sexes, with an overlap of 890 (38%) CpG sites with an a cohort submitted to gestational stress exposition. Using externals datasets, we found that the DMSs were enriched within brain modules of co-methylated CpGs during gestation and were also differentially methylated in the brain comparing boys and girls during brain development. Genes associated to the DMSs were enriched for neurodevelopmental disorders. Accordingly, we described an enrichment of the DMSs among the differentially methylated CpG sites in brain tissue between schizophrenics and controls. Here, we suggest that gender changes methylation in the autosomes working as a primary driver to stress exposition which potentially contributes for gender differences found in psychiatric outcomes.
2017-05-01 | GSE85042 | GEO
Project description:One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), tissues from 5 (skeletal muscle) or 10 (liver or SCN) wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected and run as independent replicates. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ul RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at â80 degrees C until use. Keywords: SuperSeries This reference Series links data in the following related Series: GSE3746 Circadian skeletal muscle_wt and Clock mutants GSE3748 Circadian liver_wt and Clock mutants
2010-06-12 | E-GEOD-3751 | biostudies-arrayexpress
Project description:The maternal and paternal genomes play different roles in mammalian brains as a result of genomic imprinting, an epigenetic regulation leading to differential expression of the parental alleles of some genes. Here we investigate genomic imprinting in the cerebellum using a newly developed Bayesian statistical model that provides unprecedented transcript-level resolution. We uncover 160 imprinted transcripts, including 41 novel and independently validated imprinted genes. Strikingly, many genes exhibit parentally biased -rather than monoallelic- expression, with different magnitudes according to age, organ, and brain region. Developmental changes in parental bias and overall gene expression are strongly correlated, suggesting combined roles in regulating gene dosage. These findings reveal the remarkable complexity of genomic imprinting, with important implications for understanding the normal and diseased brain. 48 samples of F1 mouse hybrids produced by crossing C57Bl/6J males with Cast/EiJ females (denoted as F1i) and reciprocally crossing Cast/EiJ males and C57Bl/6J famales (denoted as F1r).
2015-07-07 | E-GEOD-67556 | biostudies-arrayexpress