E-MTAB-9045
Ontology highlight
ABSTRACT:
DISEASE(S): Normal,Cornelia De Lange Syndrome
PROVIDER: E-MTAB-9045 | ExpressionAtlas | 2025-01-16
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:We used SLIC-CAGE to map transcriptional start sites in cortical neurons from Cornelia de Lange Syndrome (CdLS) patients and control individuals. SLIC-CAGE was performed using nuclear RNA isolated from pre-frontal cortical grey matter. Usage of nuclear RNA allows enrichment of unstable RNAs, such as RNA originating from enhancer transcription. We characterised promoter-level gene expression in cortical neurons from CdLS patients and found deregulation of hundreds of genes enriched for neuronal functions.
2021-02-27 | E-MTAB-9045 | biostudies-arrayexpress
Project description:Nuclear SLIC-CAGE of human cortical neurons from Cornelia de Lange Syndrome patients and control individuals
| PRJEB38243 | ENA
Project description:Monogenic neurodevelopmental disorders provide key insights into the pathogenesis of disease and help us understand how specific genes control the development of the human brain. Timothy syndrome is caused by a missense mutation in the L-type calcium channel Cav1.2 that is associated with developmental delay and autism. We generated cortical neuronal precursor cells and neurons from induced pluripotent stem cells derived from individuals with Timothy syndrome. Cells from these individuals have defects in calcium (Ca2+) signaling and activity-dependent gene expression and show abnormalities in differentiation. Neurons from individuals with Timothy syndrome show increased expression of markers of the upper cortical layer and decreased expression of callosal projection markers. In addition, the mutation that causes Timothy syndrome leads to an increase in the production of neurons that synthesize norepinephrine and dopamine. This phenotype can be reversed by treatment with roscovitine, a cyclin-dependent kinase and atypical L-type–channel blocker. These findings provide strong evidence that Cav1.2 regulates the differentiation of cortical neurons in humans and offer new insights into the causes of autism in individuals with Timothy syndrome. Total RNA was isolated from control and TS cells: fibroblasts, iPSCs, neurospheres (at day 7 in suspension), neurons at rest (day 45 of differentiation) and neurons kept in 67mM KCl for 9h. For sample titles, D1,D2 and D3 represent independent differentiation experiments. The number after - represents the iPSC cell line number. GSE25542_non-normalized.txt.gz contains data for 5 outliers.
2011-11-07 | E-GEOD-25542 | biostudies-arrayexpress
Project description:Monogenic neurodevelopmental disorders provide key insights into the pathogenesis of disease and help us understand how specific genes control the development of the human brain. Timothy syndrome is caused by a missense mutation in the L-type calcium channel Cav1.2 that is associated with developmental delay and autism. We generated cortical neuronal precursor cells and neurons from induced pluripotent stem cells derived from individuals with Timothy syndrome. Cells from these individuals have defects in calcium (Ca2+) signaling and activity-dependent gene expression and show abnormalities in differentiation. Neurons from individuals with Timothy syndrome show increased expression of markers of the upper cortical layer and decreased expression of callosal projection markers. In addition, the mutation that causes Timothy syndrome leads to an increase in the production of neurons that synthesize norepinephrine and dopamine. This phenotype can be reversed by treatment with roscovitine, a cyclin-dependent kinase and atypical L-type–channel blocker. These findings provide strong evidence that Cav1.2 regulates the differentiation of cortical neurons in humans and offer new insights into the causes of autism in individuals with Timothy syndrome.
2011-11-07 | GSE25542 | GEO
Project description:It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA-rearrangements in the human neocortex. We show here that neither is the case, using immunohistochemistry, transcriptome-, genome- and ploidy-analyses, and determination of nuclear bomb test-derived 14C-concentration in neuronal DNA. A large proportion of cortical neurons display DNA-fragmentation and DNA-repair short time after stroke, whereas neurons at chronic stages after stroke show DNA-integrity, demonstrating the relevance of an intact genome for survival. Analyze of potential fusion transcripts in 13 samples, seven cortical ischemic stroke tissue and six control cortex, by deep sequencing using Illumina HiSeq 2000
2014-03-28 | E-GEOD-56267 | biostudies-arrayexpress
Project description:Nucleocytoplasmic transport defects have been observed in Alzheimer’s disease (AD) and frontotemporal dementia (FTD). However, there have been few systematic efforts to evaluate transcriptome-wide subcellular mRNA distribution in these conditions, which if deregulated may significantly compromise cellular homeostasis. Here, we assessed mRNA nucleocytoplasmic localization by performing transcriptome-wide profiling on nuclear and cytoplasmic fractions of human iPSC-derived cortical neurons from healthy individuals compared to those from both familial AD and FTD patients. Our findings revealed that AD and FTD mutations induce significant changes in mRNA nucleocytoplasmic distribution. We additionally reveal the redistribution of mitochondrial-related transcripts across different mutations. The significant ‘leakage’ of mitochondrial RNA (mtRNA) into the cytosol in AD and FTD mutant neurons motivated us to examine the leakage of mtDNA. Importantly, we found abnormal cytoplasmic accumulation of mtDNA in AD and FTD cortical neurons, which is reversible with treatment using a pharmacological inhibitor of the VCP D2 ATPase domain.
2025-06-27 | GSE277599 | GEO
Project description:Smith-Magenis syndrome (SMS) is a genomic disorder caused by the deletion of a chromosomal region at 17p11.2. Individuals with SMS are frequently diagnosed with autism and have profound cortical deficits, including reduced cortex volume, mild ventriculomegaly, and epilepsy. Here, we developed human induced pluripotent stem cell (hiPSC)-derived neuronal models to understand how del(17)p11.2 affects cortical development. Hi-C identified local fusion and global reorganization of topological domains, as well as genome-wide miswiring of chromatin 3-dimensional (3D) interactions in SMS hiPSC and 3D cortical organoids. Single-nucleus RNA-seq of SMS cortical organoids identified neuropsychiatric disease-enriched transcriptional signatures and dysregulation of genes involved in catabolic and biosynthetic pathways, cell cycle processes, and neuronal signalling. SMS cortical organoids had reduced growth, enlarged ventricles, and impaired cell cycle progression. In a complementary hiPSC-derived 2D cortical neuronal model, we found SMS cortical neurons had accelerated dendritic growth, followed by neuronal hyperexcitability that was associated with a reduced potassium conductance. Our study demonstrates that del(17)p11.2 disrupts multiple steps of human cortical development, from chromatin wiring, transcriptional regulation, cell cycle progression, and morphological maturation to neurophysiological properties, and hiPSC-derived models recapitulate key neuroanatomical and neurophysiological features of SMS.
2025-08-28 | GSE295166 | GEO
Project description:To understand how NSD1 inactivation deregulates transcription, and to explore how this transcriptional deregulation affect human development, we profiled transcription in Sotos syndrome patients and healthy control individuals.
2022-03-01 | GSE191274 | GEO
Project description:Layer II stellate neurons (entorhinal cortex) and layer III cortical neurons (hippocampus CA1, middle temporal gyrus, posterior cingulate, superior frontal gyrus, primary visual cortex) were gene expression profiled. Brain regions are from individuals who had been diagnosed with mild cognitive impairment. Experiment Overall Design: ~500 neurons were selected from each of 6 brain regions. Total RNA was isolated from each batch of neurons, double round amplified, and hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays.
2009-09-05 | E-GEOD-9770 | biostudies-arrayexpress
Project description:Kabuki Syndrome (KS) is a multisystemic rare disorder, characterized by growth delay, distinctive facial features, intellectual disability, and rarely autism spectrum disorder. This condition is mostly caused by de novo mutations of KMT2D, encoding a catalytic subunit of the COMPASS complex involved in enhancer regulation. KMT2D catalyzes the deposition of histone-3-lysine-4 mono-methyl (H3K4Me1) that marks active and poised enhancers. To assess the impact of KMT2D mutations in the chromatin landscape of KS tissues, we have generated patient-derived induced pluripotent stem cells (iPSC), which we further differentiated into neural crest stem cells (NCSC), mesenchymal stem cells (MSC) and cortical neurons (iN). In addition, we further collected blood samples from 5 additional KS patients. To complete our disease modeling cohort we generated an isogenic KMT2D mutant line from human embryonic stem cells, which we differentiated into neural precursor and mature neurons. Micro-electrode-array (MEA)-based neural network analysis of KS iNs revealed an altered pattern of spontaneous network-bursts in a Kabuki-specific pattern. RNA-seq profiling was performed to relate this aberrant MEA pattern to transcriptional dysregulations, revealing that dysregulated genes were enriched for neuronal functions, such as ion channels, synapse activity, and electrophysiological activity. Here we show that KMT2D haploinsufficiency tends to heavily affect the transcriptome of cortical neurons and differentiated tissues while sparing multipotent states, suggesting that KMT2D has a most prevalent role in terminally differentiated cell and activate transcriptional circuitry unique to each cell type. Moreover, thorough profiling of H3K4Me1 unveiled the almost complete uncoupling between this chromatin mark and the regulatory effects of KMT2D on transcription, which is instead reflected by a defect of H3K27Ac. By integrating RNA-seq with ChIP-seq data we defined TEAD and REST as the master effectors of KMT2D haploinsufficiency. Also, we identified a subset of genes whose regulation is controlled by the balance between KMT2D and EZH2 dosage. Finally, we identified the bona fide direct targets of KMT2D in healthy and KS mature cortical neurons and TEAD2 as the main proxy of KMT2D dysregulation in KS. Overall, our study provides the transcriptional and epigenomic characterization of patient-derived tissues as well as iPSCs and differentiated disease-relevant cell types, as well as the identification of KMT2D direct target in cortical neurons, together with the identification of a neuronal phenotype of the spontaneous electrical activity.
2024-06-30 | E-MTAB-10561 | biostudies-arrayexpress