E-MTAB-4840
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ABSTRACT:
PROVIDER: E-MTAB-4840 | ExpressionAtlas | 2019-05-15
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:The Human Developmental Biology Resource (HDBR) expression resource is a new resource for studying prenatal human brain development. It consists of two parts which have been uploaded as two submissions: HDBR expression resource- RNAseq (E-MTAB-4840, this submission) and HDBR expression resource- SNP data (E-MTAB-4843). It is unique in the age range (4 post conception weeks [PCW] to 17PCW) and number of brains studied, particularly those under 8PCW. It is also unique in that both the large-scale data sets and the corresponding RNA and DNA samples are available, the latter via the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR; http://www.hdbr.org). There are 628 RNA-seq datasets from different regions of the brains studied. The number of regions depends on the stage and size of the sample and/or the tissue available. Embryos (4-8PCW) have been staged using a modified Carnegie staging system, details can be found at http://database.hudsen.eu/. All the RNAseq datasets from the same brain have the same embryo/fetus number (e.g. RNAseq datasets HDBR251-HDBR254 are from different tissues from embryo number 1406). The embryo/fetus ID number is recorded in the individual column. The majority of the brains studied are between 4 and 12PCW. During this time the major brain regions are established and there are the early stages of cortex development. DNA was prepared from all the tissues used for RNA-seq analysis and SNP genotype data generated from one tissue from each brain. RNA-seq data and SNP-data from the same tissue and brain have the same name (e.g. HDBR469). There are also SNP genotype data from 229 additional specimens in paraffin wax blocks available for individual gene expression studies. These data are in the accompanying HDBR expression resource- SNP data (E-MTAB-4843).
2016-10-12 | E-MTAB-4840 | biostudies-arrayexpress
Project description:The Human Developmental Biology Resource (HDBR) expression resource is a new resource for studying prenatal human brain development. It consists of two parts which have been uploaded as two submissions: HDBR expression resource- RNAseq (E-MTAB-4840) and HDBR expression resource- SNP data (E-MTAB-4843, this submission). It is unique in the age range (4 post conception weeks [PCW] to 17PCW) and number of brains studied, particularly those under 8PCW. It is also unique in that both the large-scale data sets and the corresponding RNA and DNA samples are available, the latter via the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR; www.hdbr.org). There are 628 RNA-seq datasets from different regions of the brains studied. The number of regions depends on the stage and size of the sample and/or the tissue available. Embryos (4-8PCW) have been staged using a modified Carnegie staging system, details can be found at http://database.hudsen.eu/. All the RNAseq datasets from the same embryo/fetus have the same ID number (e.g. RNAseq datasets HDBR251-HDBR254 are from different tissues from embryo number 1406). The embryo/fetus ID number is recorded in the âindividualâ column. The majority of the brains studied are between 4 and 12PCW. During this time the major brain regions are established and there are the early stages of cortex development. DNA was prepared from all the tissues used for RNA-seq analysis and SNP genotype data generated from one tissue from each brain. RNA-seq data and SNP-data from the same tissue and individual embryo or fetus have the same name (e.g. HDBR469). There are also SNP genotype data from 229 additional specimens in paraffin wax blocks available for individual gene expression studies. For the specimens in wax blocks, the SNP genotype data was generated from DNA from either skin or placenta. The tissues present in the corresponding wax block(s) are given in the biosource type column.
2016-10-12 | E-MTAB-4843 | biostudies-arrayexpress
Project description:Human Developmental Biology Resource (HDBR) expression resource-RNAseq
| PRJEB14594 | ENA
Project description:<p>Non-coding elements in our genomes that play critical roles in complex disease are frequently marked by highly unstable RNA species. Sequencing nascent RNAs attached to an actively transcribing RNA polymerase complex can identify unstable RNAs, including those templated from gene-distal enhancers (eRNAs). However, nascent RNA sequencing techniques remain challenging to apply in some cell lines and especially to intact tissues, limiting broad applications in fields such as cancer genomics and personalized medicine. Here we report the development of chromatin run-on and sequencing (ChRO-seq), a novel run-on technology that maps the location of RNA polymerase using virtually any frozen tissue sample, including samples with degraded RNA that are intractable to conventional RNA-seq. We used ChRO-seq to develop the first maps of nascent transcription in 23 human glioblastoma (GBM) brain tumors and patient derived xenografts. Remarkably, >90,000 distal enhancers discovered using the signature of eRNA biogenesis within primary GBMs closely resemble those found in the normal human brain, and diverge substantially from GBM cell models. Despite extensive overall similarity, 12% of enhancers in each GBM distinguish normal and malignant brain tissue. These enhancers drive regulatory programs similar to the developing nervous system and are enriched for transcription factor binding sites that specify a stem-like cell fate. These results demonstrate that GBMs largely retain the enhancer landscape associated with their tissue of origin, but selectively adopt regulatory programs that are responsible for driving stem-like cell properties. We also identified enhancers and their associated transcription factors that regulate genes characteristic of each known GBM subtype, and discovered a core group of transcription factors that control the expression of genes associated with clinical outcomes. This study uncovers new insights into the molecular etiology of GBM and introduces ChRO-seq which can now be used to map regulatory programs contributing to a variety of complex diseases.</p>
| phs001646 | dbGaP
Project description:During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the post-transcriptional control of gene expression and protein abundance during human corticogenesis remains poorly understood. We addressed this issue by using a dual reporter cell line to isolate neural progenitors and neurons from the telencephalic brain organoid tissue and performed cell type and developmental stage-specific transcriptome and proteome analysis. Integrating the two datasets revealed temporal modules of gene expression during human corticogenesis, both at RNA and protein level. Our multiomics approach reveals novel posttranscriptional regulatory mechanisms crucial for fidelity of cortical development.
2022-10-25 | PXD037106 | Pride
Project description:The postsynaptic density (PSD) contains a collection of scaffold proteins used for the assembly of synaptic signaling complexes and disruption of this signaling machinery might be implicated in a variety of brain disorders. However, it is not known how the core-scaffold machinery associates this collection of proteins through development and how proteins coding for genes involved in psychiatric and other brain disorders are distributed through spatio-temporal protein complexes. Here, using immunopurification, proteomics, bioinformatics and mouse genetics, we isolated 2876 proteins across 41 in-vivo protein complexes and determined their protein domain composition, correlation to gene expression levels, and developmental integration to the PSD. We defined major protein clusters for enrichment of schizophrenia (SCZ), autism spectrum disorders (ASD), developmental delay (DD), and intellectual disability (ID) risk factors at embryonic day 14 and the adult PSD. These protein complexes contained a discrete number of protein domains defining molecular functions. Mutations in highly-connected nodes alter protein-protein interactions that modulate the assembly of macromolecular complexes enriched in disease risk candidates. These results were integrated into a software platform: Synaptic Protein/Pathways Resource (SyPPRes), enabling the prioritization of brain disease risk factors and their placement within synaptic protein interaction networks.
2017-08-22 | PXD006277 | Pride
Project description:The precise regulation of gene expression is fundamental to neurodevelopment, plasticity, and cognitive function. While several studies have profiled transcription in the developing human brain, there is a gap in our understanding of accompanying translational regulation. We performed ribosome profiling on 73 human prenatal and adult cortex samples. We characterized the translational regulation of annotated open reading frames (ORFs) and identified thousands of previously unknown translation events, including small ORFs that give rise to human- and/or brain-specific microproteins, many of which we independently verified using proteomics. Ribosome profiling in stem cell-derived human neuronal cultures corroborated these findings and revealed that several neuronal activity-induced non-coding RNAs encode previously undescribed microproteins. Physicochemical analysis of brain microproteins identified a class of proteins that contain arginine-glycine-glycine (RGG) repeats and thus may be regulators of RNA metabolism. This resource expands the known translational landscape of the human brain and illuminates previously unknown brain-specific protein products.
2022-09-29 | PXD035950 | Pride
Project description:The complexity of the mature adult brain is a result of both developmental processes and experience-dependent circuit formation. One way to look at the process of brain development is to examine gene expression changes, and previous studies have used microarrays to address this in a global manner. However, the transcriptome is more complex than gene expression levels alone, as both alternative splicing and RNA editing occur to generate a more diverse set of mature transcripts. The aim of the current study was to develop a high-resolution transcriptome dataset of mouse cortical development using RNA sequencing (RNA-Seq), thus assaying exon usage and RNA editing as well as overcoming some of the inherent limitations of microarrays. We found a large number of differentially expressed genes, but also altered splicing and RNA editing between embryonic and adult cerebral cortex. Each dataset was validated both technically and biologically, and in each case tested we found our RNA-Seq observations to have high predictive validity. We propose this dataset, and the accompanying analysis, to be a helpful resource in the understanding of changes in gene expression during development. Three young adult cerebral cortices four embryonic cerebral cortices
2013-02-10 | E-GEOD-39866 | biostudies-arrayexpress
Project description:<p>Defining the number, proportion, or lineage of distinct cell types in the developing human brain is an important goal of modern brain research. We produced single cell transcriptomic profiles for 40,000 cells at mid-gestation to define deep expression profiles corresponding to all known major cell types at this developmental period and compare this with bulk tissue profiles. We identified multiple transcription factors (TFs) and co-factors expressed in specific cell types, including multiple new cell-type-specific relationships, providing an unprecedented resource for understanding human neocortical development and evolution. This includes the first single-cell characterization of human subplate neurons and subtypes of developing glutamatergic and GABAergic neurons. We also used these data to deconvolute single cell regulatory networks that connect regulatory elements and transcriptional drivers to single cell gene expression programs in the developing CNS. We characterized major developmental trajectories that tie cell cycle progression with early cell fate decisions during early neurogenesis. Remarkably, we found that differentiation occurs on a transcriptomic continuum, so that differentiating cells not only express the few key TFs that drive cell fates, but express broad, mixed cell-type transcriptomes prior to telophase. Finally, we mapped neuropsychiatric disease genes to specific cell types, implicating dysregulation of specific cell types in ASD, ID, and epilepsy, as the mechanistic underpinnings of several neurodevelopmental disorders. Together these results provide an extensive catalog of cell types in human neocortex and extend our understanding of early cortical development, human brain evolution and the cellular basis of neuropsychiatric disease.</p>
| phs001836 | dbGaP
Project description:Long noncoding RNAs (lncRNAs) have been described in cell lines and various whole tissues, but lncRNA analysis of development in vivo is limited. Here, we comprehensively analyze lncRNA expression for the adult mouse subventricular zone neural stem cell lineage. We utilize complementary genome-wide techniques including RNA-seq, RNA CaptureSeq, and ChIP-seq to associate specific lncRNAs with neural cell types, developmental processes, and human disease states. By integrating data from chromatin state maps, custom microarrays, and FACS purification of the subventricular zone lineage, we stringently identify lncRNAs with potential roles in adult neurogenesis. shRNA-mediated knockdown of two such lncRNAs, Six3os and Dlx1as, indicate roles for lncRNAs in the glial-neuronal lineage specification of multipotent adult stem cells. Our data and workflow thus provide a uniquely coherent in vivo lncRNA analysis and form the foundation of a user-friendly online resource for the study of lncRNAs in development and disease. RNA-seq (both paired end and single) from the adult neurogenic niches- subventricular zone (SVZ), olfactory bulb (OB), dentate gyrus (DG) and control non-neurogenic tissue, striatum (STR). Reads were used to assemble a lncRNA catalogue and determine expression values for both protein-coding and noncoding genes
2013-04-11 | E-GEOD-45278 | biostudies-arrayexpress