Project description:DNA methylation profiling of Prefrontal Cortex of male rats at postnatal day 62 whose mothers were exposed to restraint stress from gestation day 14 until delivery The groups consist of 1. Control rats (Ctrl) 2. Prenatally stressed rats (PNS)
Project description:There is increasing recognition about the importance of epigenetic dysregulation in neurodevelopmental disorders including autism spectrum disorder and schizophrenia, yet little is known about patterns of gene regulation in the later stages of fetal development and the first decade of life. In this study we profiled changes in DNA methylation, an epigenetic modification to cytosine involved in mediating the developmental regulation of gene expression and function, across human brain development in cortex tissue from 107 human fetal and child donors spanning 6 post-conceptual weeks to 8 years old.
Project description:DNA methylation profiling of Prefrontal Cortex of male rats at postnatal day 62 whose mothers were exposed to restraint stress from gestation day 14 until delivery
Project description:JMML (Juvenile myelomonocytic leukaemia) is a leukaemia hat only develops in young children and is thought to have a prenatal initiation. To study the relationship between JMML and normal ontogeny we studied the transcriptome of HSPC (hematopoietic stem and progenitor cells) sorted from sporadic JMML patients, healthy prenatal samples and from healthy age matched donors. Bulk transcriptome of sorted HSPC reveals that some JMML samples cluster with prenatal samples whereas other from a distinct cluster apart from any healthy samples. Methylation profile on bulk mononucleated cell on theses JMML patients, 2 healthy postnatal and 2 healthy prenatal samples is also investigated. The results show a global hypermethylation in JMML samples compared to healthy samples and a specific JMML group with a hypermethylated profile compared to all JMML samples.
Project description:Prenatal exposure to infectious or inflammatory insults can increase the risk of neuropsychiatric disorders with neurodevelopmental components, including schizophrenia and autism. The molecular processes underlying this pathological association are only partially understood. Here, we implemented an unbiased genome-wide transcriptional profiling of the prefrontal cortex of mice exposed to prenatal infection on GD17 compared to control subjects in order to elucidate the long term molecular signature of late prenatal infection. We used microarray analysis to investigate the long lasting gene expression changes in a well-established mouse model that is based on maternal treatment with the viral mimic poly(I:C) during pregnancy C57BL/6 mice were treated with the synthetic viral mimetic poly(I:C) (5 mg/kg, i.v.) or control (saline, i.v.) solution on gestation day 17. Offspring were subjected to cognitive and behavioral testing in adulthood, and then whole genome gene expression analysis with Affymetrix Microarray and subsequent q-PCR validation were performed on the prefrontal Cortex.
Project description:There is increasing recognition about the importance of epigenetic dysregulation in neurodevelopmental disorders including autism spectrum disorder and schizophrenia, although the cell-type specific changes in gene regulation across critical periods of brain development have not been fully elucidated. In this study we profiled DNA methylation of purified populations of neuronal (SATB2+) and non-neuronal (SATB2-) cell-types in 47 human fetal and child donors (8 post-conceptual weeks to 8 years old).
Project description:DNA methylation (DNAm) is important in brain development, and potentially in schizophrenia. We characterized DNAm in prefrontal cortex from 335 non-psychiatric controls across the lifespan and 191 patients with schizophrenia, and identified widespread changes in the transition from prenatal to postnatal life. These DNAm changes manifest in the transcriptome, correlate strongly with a shifting cellular landscape, and overlap regions of genetic risk for schizophrenia. A quarter of published GWAS-suggestive loci (4,208/15,930, p<10-20) manifest as significant methylation quantitative trait loci (meQTLs), including 59.6% of GWAS-positive schizophrenia loci. We identified 2,104 CpGs that differ between schizophrenia patients and controls, enriched for genes related to development and neurodifferentiation. The schizophrenia-associated CpGs strongly correlate with changes related to the prenatal-postnatal transition and show slight enrichment for GWAS risk loci, while not corresponding to CpGs differentiating adolescence from later adult life. These data implicate an epigenetic component to the developmental origins of this disorder.
Project description:The prefrontal cortex (PFC) is a core regulatory center for higher cognitive functions in the mammalian brain. In early postnatal mice, the PFC remains incompletely mature, particularly the intratelencephalic (IT) neurons located in superficial layers. However, the molecular developmental trajectories and regulatory mechanisms of IT neurons during the critical postnatal period (1-2 weeks) for circuit establishment, remain poorly characterized at single-cell resolution. Here, we performed single-cell RNA sequencing analysis on mouse PFC isolated at different developmental time points, and integrated with spatial transcriptomic data. Our study systematically deciphered the spatiotemporal transcriptome dynamics of mouse PFC during postnatal development, with particular emphasis on the heterogeneity of IT neurons. We identified dynamically expressed genes during postnatal development, including cadherin and axon guidance molecule genes, as well as specific transcriptional regulators that control the maturation of IT neurons in different layers. Furthermore, we also revealed that glial cells play crucial regulatory roles in IT neuron development through specific signaling pathways. Our study provides a comprehensive single-cell atlas of postnatal mouse PFC development, offering important insights into the mechanisms of neural development and circuit assembly in PFC.
Project description:We report the first full transcriptome analysis of layer II and deep layers of the medial and lateral entorhinal cortex during postnatal development. Our analysis showed that postnatal timepoint was the most important element in entorhinal cortex transcriptional dynamics, followed by laminar differences. There were fewer differentially expressed genes between the medial and lateral parts of the entorhinal cortex, and most of these were found in layer II.