Fetal origin of sex-bias brain aging [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA888983 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21851085_1.fastq.gz | Fastqsanger.gz | |||
| SRR21851085_2.fastq.gz | Fastqsanger.gz | |||
| SRR21851086_1.fastq.gz | Fastqsanger.gz | |||
| SRR21851086_2.fastq.gz | Fastqsanger.gz | |||
| SRR21851087_1.fastq.gz | Fastqsanger.gz |
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Project description:Fetal origin of sex-bias brain aging
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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.
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Project description:In this study, gene expression of brain from postnatal (day 5) and aging (week 70) mice (C57BL/6J) was profiled. The data was used to infer transcriptional network of genes associated with epigenetic clock and GnRHR pathway in the brain. The results of this study suggested that brain aging originated early-in life.
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Project description:Benchmark of RNA-seq in fetal growth restriction pregnancies with sex bias
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Project description:Bacterial and viral infections of the placenta are associated with inflammation and adverse pregnancy outcomes. Hofbauer cells (HBCs) are specialised fetal-origin macrophages in the placental villi and are proposed to protect the fetus from vertical transmission of pathogens; however, they are poorly understood. Here, we have performed quantitative proteomics on term HBCs under resting conditions and following exposure to bacterial and viral pathogen associated molecular patterns (PAMPs), and investigated the contribution of fetal sex to these responses. Resting HBCs expressed a plethora of proteins pertinent to macrophage function, including chemokines, cytokines, Toll-like receptors, and classical and non-classical major histocompatibility complex class I and II molecules. HBCs mounted divergent responses to bacterial versus viral PAMPs but exhibited protein expression changes suggestive of a switch towards a more pro-inflammatory phenotype. A comparison between male and female HBCs, showed that the latter mounted a much stronger and wider response. Sexual dimorphism in HBCs was primarily associated with lipid metabolism in males and cytoskeleton organisation in females. We provide a novel and comprehensive understanding regarding the phenotype of term placental macrophages and their sex-dependent responses to infectious triggers.
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Project description:To investigate the epigenetic landscape at the interface between mother and fetus, we provide a comprehensive analysis of parent of origin bias in the placenta. Using F1 interspecies hybrids, we sequenced RNA from 23 individual midgestation placentas, five late stage placentas, and two yolk sac samples and then used SNPs to determine whether transcripts were preferentially generated from the maternal or paternal allele. In the placenta, we find 103 genes that show significant and reproducible parent-of-origin bias, of which 78 are novel candidates. Most (96%) show a strong maternal bias which, using multiple models, we demonstrate is not due to maternal decidual contamination. Analysis of the X chromosome also reveals paternal expression of Xist and several genes that escape inactivation, most significantly Rps4x, Fhl1, and Slc38a5. Finally, sequencing individual placentas allowed us to reveal notable expression similarity between littermates. In all, we observe a striking preference for maternal transcription in the midgestation mouse placenta and a dynamic imprinting landscape in extraembryonic tissues, reflecting the complex nature of epigenetic pathways in the placenta. 3'-end Sequencing for Expression Quantification (3SEQ) and SNP Analysis to observe parent-of-origin bias in 28 placental samples at two time points and 2 yolk sac samples
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Project description:Aging and sex have a strong influence on the functional capacity of the immune system. In general, the immune response in females is stronger than that in males, but there is little information about the effect of aging on this difference. To address this question, we performed a transcriptomic analysis of peripheral blood mononuclear cells derived from nonagenarians and young controls. We found 337 and 269 genes to be differentially expressed (p<0.05, fold change >1.5 or <-1.5) in nonagenarian females and males, respectively; 177 of these were changed in both sexes. An analysis of the affected signaling pathways revealed a clear sex bias: the number of significantly changed pathways was 43 in females and 40 in males; 23 were shared. These data show that the effects of aging on the immune system are significantly different in males and females.
2015-01-22 | GSE65219 | GEO
Project description:Aging and sex have a strong influence on the functional capacity of the immune system. In general, the immune response in females is stronger than that in males, but there is little information about the effect of aging on this difference. To address this question, we performed a transcriptomic analysis of peripheral blood mononuclear cells derived from nonagenarians and young controls. We found 337 and 269 genes to be differentially expressed (p<0.05, fold change >1.5 or <-1.5) in nonagenarian females and males, respectively; 177 of these were changed in both sexes. An analysis of the affected signaling pathways revealed a clear sex bias: the number of significantly changed pathways was 43 in females and 40 in males; 23 were shared. These data show that the effects of aging on the immune system are significantly different in males and females. Our study population consisted of 146 nonagenarians (103 females, 43 males) and 30 young controls (19-30 years of age, 21 females, 9 males). In our study, we analyzed the gene expression difference between nonagenarian and control women as well as between nonagenarian and control males and then compared these results.
2013-01-10 | E-GEOD-40366 | biostudies-arrayexpress
Project description:Aging and sex have a strong influence on the functional capacity of the immune system. In general, the immune response in females is stronger than that in males, but there is little information about the effect of aging on this difference. To address this question, we performed a transcriptomic analysis of peripheral blood mononuclear cells derived from nonagenarians and young controls. We found 337 and 269 genes to be differentially expressed (p<0.05, fold change >1.5 or <-1.5) in nonagenarian females and males, respectively; 177 of these were changed in both sexes. An analysis of the affected signaling pathways revealed a clear sex bias: the number of significantly changed pathways was 43 in females and 40 in males; 23 were shared. These data show that the effects of aging on the immune system are significantly different in males and females. Our study population consisted of 146 nonagenarians (103 females, 43 males) and 30 young controls (19-30 years of age, 21 females, 9 males). In our study, we analyzed the gene expression difference between nonagenarian and control women as well as between nonagenarian and control males and then compared these results.
2015-01-22 | E-GEOD-65219 | biostudies-arrayexpress
Project description:To investigate the epigenetic landscape at the interface between mother and fetus, we provide a comprehensive analysis of parent of origin bias in the placenta. Using F1 interspecies hybrids, we sequenced RNA from 23 individual midgestation placentas, five late stage placentas, and two yolk sac samples and then used SNPs to determine whether transcripts were preferentially generated from the maternal or paternal allele. In the placenta, we find 103 genes that show significant and reproducible parent-of-origin bias, of which 78 are novel candidates. Most (96%) show a strong maternal bias which, using multiple models, we demonstrate is not due to maternal decidual contamination. Analysis of the X chromosome also reveals paternal expression of Xist and several genes that escape inactivation, most significantly Rps4x, Fhl1, and Slc38a5. Finally, sequencing individual placentas allowed us to reveal notable expression similarity between littermates. In all, we observe a striking preference for maternal transcription in the midgestation mouse placenta and a dynamic imprinting landscape in extraembryonic tissues, reflecting the complex nature of epigenetic pathways in the placenta.
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