Expression analysis of neuronal differentiation of single mutants UBE3A/PHLDA2/SLC22A18 and double mutant PHLDA2/SLC22A18 cells
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2000
ORGANISM(S): Homo sapiens
SUBMITTER: Shay Kinreich
PROVIDER: E-MTAB-12504 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:The de novo DNA methyltransferase DNMT3B functions in establishing DNA methylation patterns during development. We performed RNAi knockdown of DNMT3B in human embryonic stem cells (ESCs) in order to investigate the mechanistic contribution of DNMT3B on DNA methylation and early neuronal differentiation. Genome-wide analyses of DNA methylation by MethylC-seq identified novel regions of hypomethylation in the DNMT3B knockdowns along the X chromosome as well as pericentromeric regions, rather than changes to specific dysregulated gene promoters. While DNMT3B was not required for early neuroepithelium specification, DNMT3B deficient neuroepithelium exhibited accelerated maturation with earlier expression of mature neuronal markers (such as NEUROD1) and early neuronal regional specifiers (such as neural crest) relative to normal ESCs. Our results suggest that DNMT3B mediates large-scale methylation patterns in human ESCs and that DNMT3B deficiency alters the timing of neuronal maturational differentiation in human neuronal cultures. Examined DNA methylation in human embryonic stem cells, both with and without DNMT3B knockdown
2012-03-27 | E-GEOD-32268 | biostudies-arrayexpress
Project description:To investigate the effects of ZIKV infection or ZIKV-NS4B-transduction on the global proteome scale at early stages of hNPC differentiation into neurons, hNPC cells were infected with ZIKV (Asian strain: H/PF/2013; MOI=0.01) or transduced with ZIKV-NS4B or HCV-NS4B and one day later cells were either left under proliferative conditions or neuronal differentiation was induced with ROCK inhibitors treatment and growth factors withdrawals. Five days later samples were harvested and processed for quantitative label-free proteomics.
2018-09-03 | PXD009557 | Pride
Project description:Development of efficient and reproducible conditions for directed differentiation of pluripotent stem cells into specific cell types is important not only to understand early human development but also to enable more practical applications, such as in vitro models of disease, drug discovery, and cell therapies. The differentiation of stem cells to retinal pigment epithelium (RPE) in particular holds promise as a source of cells for therapeutic replacement in age-related macular degeneration. Here we show development of a robust and efficient method to derive RPE with high reproducibility in an adherent, monolayer system using sequential inhibition and activation of the Activin and BMP signalling pathways. We use whole genome transcript analysis to characterize cells at different stages of differentiation to gain further understanding of the developmental dynamics and fate specification of RPE.
2016-01-15 | E-MTAB-4259 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-10-09 | E-GEOD-54726 | biostudies-arrayexpress
Project description:Whole genome expression analysis reveals that single blastomeres from day-3 human embryos and blastocysts show unique gene signature, thus hESC derived from these two developmental sources might show differential gene expression profile. Comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. hESC derived from single blastomeres (VAL-10B and VAL-11B) and from ICM (VAL-5, -7, and -8) were compared by global gene expression
2012-11-27 | E-GEOD-42520 | biostudies-arrayexpress
Project description:Schizophrenia and other psychiatric disorders are postulated to be developmental disorders resulting from synapse dysfunction. How susceptibility genes for major mental disorders could lead to synaptic deficits in humans is not well-understood. Here we generated induced pluripotent stem cells (iPSCs) from four members of a family in which a frame-shift mutation of Disrupted-in-schizophrenia-1 (DISC1) co-segregated with psychiatric disorders and further produced different isogenic iPSC lines via genetic editing. We showed that mutant DISC1 causes synaptic vesicle release deficits in iPSC-derived forebrain neurons. Mechanistically, mutant DISC1 dysregulates the expression of many genes related to synapses and psychiatric disorders and depletes wild-type DISC1 and the NCoR1 transcription co-repressor complex. Furthermore, mechanism-guided pharmacological inhibition of phosphodiesterases rescues synaptic defects in mutant neurons. Our study uncovers a novel gain-of-function mechanism through which the psychiatric disorder-relevant mutation affects synaptic functions via transcriptional dysregulation and provides insight into the molecular and synaptic etiopathology of psychiatric disorders. Two patient derived iPSC lines carrying heterozygous 4bp deletion in DISC1 gene and 1 related control were analyzed in biological triplicate
2014-08-01 | E-GEOD-57821 | biostudies-arrayexpress
Project description:Illumina TRUseq method to generate highly strand-specific next-generation sequencing (NGS) libraries
2019-03-20 | E-MTAB-5114 | biostudies-arrayexpress
Project description:Astrocytes derived from normal and aneuploid human embryonic stem cells, along with CCF-STTG1 astrocytoma cell line, and using three biological replicates for each sample, were used to develop an in-vitro model system, to identify biomarkers for astrocytic cancer cells and premalignant stem-like progenitors.<br><br>
2010-06-01 | E-MEXP-2633 | biostudies-arrayexpress
Project description:Tumor suppressor p53 promotes differentiation of human embryonic stem cells (hESCs), but an in-depth understanding of mechanism is lacking. Here, we define p53 functions in hESCs by genome wide profiling of p53 chromatin interactions and intersection with gene expression during early differentiation and in response to DNA damage. During differentiation, p53 targets and regulates a unique collection of genes, many of which encode transcription factors and developmental regulators with chromatin structure poised by OCT4 and NANOG and marked by repressive H3K27me3 in pluripotent hESCs. In contrast, genes associated with cell migration and motility are bound by p53 specifically after DNA damage. Surveillance functions of p53 in regulation of cell death and cell cycle genes are conserved during both DNA damage and differentiation. Our findings expand the registry of p53 -regulated genes in hESCs and define specific functions of p53 in opposing pluripotency, which are highly distinct from stress-induced p53 response in stem cells. Identification of p53 binding sites in hESC under three conditions: Pluripotent, DNA damaged, Differentiating
2013-10-18 | E-GEOD-39762 | biostudies-arrayexpress
Project description:Exposure to lead (Pb) during childhood can result in learning disabilities and behavioral problems. Although described in animal models, whether Pb exposure also alters neuronal differentiation in the developing brains of exposed children is unknown. Here, we investigated the effects of physiologically relevant concentrations of Pb (from 0.4 to 1.9 M-BM-5M or 0 to 40M-BM-5g/dl) on the capacity of human embryonic stem cells (hESCs) to progress to a neuronal fate. We found that neither acute nor chronic exposure to Pb prevented hESCs from generating neural precursor cells (NPCs). NPCs derived from hESCs chronically exposed to 1.9 M-BM-5M or 40M-BM-5g/dl Pb throughout the neural differentiation process generated 2.5 times more TUJ1-positive neurons than those derived from control hESCs. Pb exposure of hESCs during the stage of neural rosette formation resulted in a significant decrease in the expression levels of the neural marker genes PAX6 and MSI1. Furthermore, the resulting NPCs differentiated into neurons with shorter neurites and less branching than control neurons, as assessed by Sholl analysis. DNA methylation studies of control, acutely treated hESCs and NPCs derived from chronically exposed hESCs using the Illumina HumanMethylation450 BeadChipM-BM-. demonstrated that Pb exposure induced changes in the methylation status of genes involved in neurogenetic signaling pathways. In summary, our study shows that exposure to Pb subtly alters the neuronal differentiation of exposed hESCs and that these changes could be partly mediated by modifications in the DNA methylation status of genes crucial to brain development. We analyzed the methylation profile of undifferentiated (n=2 independent experiments) and differentiating (n=2 independent experiments) human embryonic stem cells (hESCs) acutely exposed to losed to lead (Pb) and neural precursor cells derived from hESCs chronically exposed to Pb throughout the neural differentiation process (n=3 independent experiments).
2014-02-01 | E-GEOD-54596 | biostudies-arrayexpress