Project description:In this study, gene expression was profiled by RNA-seq to examine whole transcriptome of the male and female fetal brain of domesticated pig on the three gestation days 45, 60 and 90. Gene expression in fetal brain was distinct on day 90 compared to days 45 and 60. The homeobox genes were consistently upregulated in the brain of females compared to males during development. The sex of adjacent fetuses influenced gene expression of fetal brain. Extensive exon-level expression changes in the developing brains was observed. Pathway enrichment analysis showed that the ionotropic glutamate receptor pathway and p53 pathway were enriched in female brain only whereas receptor mediated signaling pathways were enriched in the male brain alone. Genes that are known markers of neurons and astrocytes were differentially regulated in male and female brain during development. The study further suggests that regulation of ion transportation via placental matrotrophy may play a role in fetal brain development.
Project description:DNA methylation was profiled in a genome-wide manner by Enzymatic Methyl-seq (EM-seq) in fetal brain of both sexes at three gestation days 45, 60 and 90. The analysis showed nearly 3-fold fewer differentially methylated sites (DMSs) between GD90 and GD60 (n=54) compared to that between GD60 and GD45 (n=150). Comparative analysis of the methylation data with the RNA-seq data previously generated from the same gestation times showed an opposition pattern where more number of differentially expressed genes (DEGs) were observed between GD90 and GD60 compared to GD60 and GD45.
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.
Project description:This SuperSeries is composed of the following subset Series: GSE33737: Fetal programming of muscle transcriptome in response to gestational dietary protein levels in the pig [AP] GSE33738: Fetal programming of muscle transcriptome in response to gestational dietary protein levels in the pig [HP] GSE33739: Fetal programming of muscle transcriptome in response to gestational dietary protein levels in the pig [LP] Refer to individual Series
Project description:Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and gene regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains. We found that early non-CG methylation accumulation at super-enhancers in both fetal brain and organoids marks forthcoming transcriptional repression in the fully developed brain. 74% of 35,627 demethylated regions identified during organoid differentiation overlapped with fetal brain regulatory elements. Interestingly, pericentromeric repeats showed widespread demethylation in multiple types of in vitro human neural differentiation models but not in fetal brain. Our study reveals that organoids recapitulate many epigenomic features of mid-fetal human brain and also identified novel non-CG methylation signatures of brain development.
Project description:This SuperSeries is composed of the following subset Series: GSE25482: Fetal programming of hepatic transcriptome in response to gestational dietary protein levels in the pig (AP data set) GSE25483: Fetal programming of hepatic transcriptome in response to gestational dietary protein levels in the pig (HP data set) Refer to individual Series
Project description:Publication title: Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver; To investigate the role of DNA methylation during human development, we developed Methyl-seq, a method that assays DNA methylation at more than 90,000 regions throughout the genome. Performing Methyl-seq on human embryonic stem cells (hESCs), their derivatives and human tissues allowed us to identify several trends during hESC and in vivo liver differentiation. First, differentiation results in DNA methylation changes at a minimal number of assayed regions, both in vitro and in vivo (2-11%). Second, in vitro hESC differentiation is characterized by both de novo methylation and demethylation, whereas in vivo fetal liver development is characterized predominantly by demethylation. Third, hESC differentiation is uniquely characterized by methylation changes specifically at H3K27me3-occupied regions, bivalent domains and low-density CpG promoters (LCPs) suggesting that these regions are more likely to be involved in transcriptional regulation during hESC differentiation. Although both H3K27me3-occupied domains and LCPs are also regions of high variability in DNA methylation state during human liver development, these regions become highly unmethylated, which is a distinct trend from that observed in hESCs. Taken together, our results indicate that hESC differentiation has a unique DNA methylation signature that may not be indicative of in vivo differentiation. Experiment Overall Design: lumina gene expression beadchips of human ES cell lines, ES-derived cells, and normal liver (15 samples). High-throughput sequencing of ES cell lines, ES-derived cells, and fetal and normal livers (17 samples). Raw data: SRA008154 http://www.ncbi.nlm.nih.gov/sites/entrez?db=sra&cmd=search&term=SRA008154