Transcriptome analysis of CHARGE patients iPSC-derived neural stem/progenitor cells
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PROVIDER: PRJNA422715 | ENA |
REPOSITORIES: ENA
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Project description:We performed a microarray experiment to analyze the transcriptional profile of CHARGE patient iPSC-derived neural stem/progenitor cells to identify CHD7 target genes.
2018-03-28 | GSE108170 | GEO
Project description:CHARGE syndrome is caused by heterozygous mutations in a chromatin remodeler CHD7 and characterized by a set of malformations historically postulated to arise from defects in the neural crest formation during embryogenesis. To better delineate neural crest defects in CHARGE syndrome, we generated induced pluripotent stem cells (iPSCs) from two patients with typical syndrome manifestations, and characterized neural crest cells differentiated in vitro from these iPSCs (iPSC-NCCs). We found that expression of genes associated with cell migration was altered in CHARGE iPSC-NCCs as compared to control iPSC-NCCs. Consistently, CHARGE iPSC-NCCs showed defective delamination, migration and motility in vitro, and their transplantation in ovo revealed overall defective migratory activity in the chick embryo. Altogether, our results support the historical inference that CHARGE syndrome patients have defects in neural crest migration and provide the first successful application of patient-derived iPSCs in modeling craniofacial disorders.
2017-10-23 | GSE86212 | GEO
Project description:Mitochondrial DNA (mtDNA) mutations predominantly cause neurological diseases. Searching for therapeutic strategies is hindered by the absence of viable neural model systems due to the challenges of engineering mtDNA. We demonstrate that neural progenitor cells (NPCs), rapidly obtained from human induced pluripotent stem cells (iPSCs), retain the parental mtDNA profile and exhibit mitochondrial maturation coupled with a metabolic switch away from glycolysis. Altered calcium homeostasis and mitochondrial hyperpolarization, both potential causes of neural impairment, were observed in iPSC-derived NPCs from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C). Phenotype-based high-content screenings (HCS) with FDA-approved compounds were carried out, leading to the identification of possible innovative counteracting agents. We propose iPSC-derived NPCs, displaying mild proliferative properties and proper genotype/metabotype, as a bona fide model system for the establishment of personalized phenotypic drug discovery for untreatable mtDNA disorders affecting the nervous system. Associated GEO accession number: GSE70071.
2017-01-31 | PXD004977 | Pride
Project description:Mitochondrial DNA (mtDNA) mutations predominantly cause neurological diseases. Searching for therapeutic strategies is hindered by the absence of viable neural model systems due to the challenges of engineering mtDNA. We demonstrate that neural progenitor cells (NPCs), rapidly obtained from human induced pluripotent stem cells (iPSCs), retain the parental mtDNA profile and exhibit mitochondrial maturation coupled with a metabolic switch away from glycolysis. Altered calcium homeostasis and mitochondrial hyperpolarization, both potential causes of neural impairment, were observed in iPSC-derived NPCs from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C). Phenotype-based high-content screenings (HCS) with FDA-approved compounds were carried out, leading to the identification of possible innovative counteracting agents. We propose iPSC-derived NPCs, displaying mild proliferative properties and proper genotype/metabotype, as a bona fide model system for the establishment of personalized phenotypic drug discovery for untreatable mtDNA disorders affecting the nervous system. Associated GEO accession number: GSE70071.
2017-03-31 | MSV000080849 | MassIVE
Project description:Our purpose was to investigate genes and molecular mechanisms involved in patients with Leber congenital amaurosis (LCA). Fibroblasts from two unrelated clinically-identified patients (Coriell) were reprogrammed to pluripotency by retroviral transduction. These human induced Pluripotent Stem Cells (hiPSCs) were differentiated into neural stem cells (NSC) that mimicked the neural tube stage and retinal pigmented epithelial (RPE) cells that could be targeted by the disease. A genome wide transcriptome analysis was performed with Affymetrix Exon Array GeneChipM-BM-., comparing LCA-hiPSCs derivatives to controls. The aim was to identify differentially expressed genes which may be associated with early developmental defect before the establishment of mature retinal circuitry. We analyzed iPSC-derived neural stem cells from LCA patient's fibroblast (n=2) and iPSC-derived neural stem cells from healthy people fibroblast (n=2). A total of 21 samples were analyzed : 9 NSC derived from iPSC LCA and 12 NSC derived from wild-type iPSC.
2015-01-21 | E-GEOD-43924 | biostudies-arrayexpress
Project description:Autism spectrum disorder (ASD) is an early onset neurodevelopmental disorder, which is characterized by disturbances of brain function and behavioral deficits in core areas of impaired reciprocal socialization, impairment in communication skills, and repetitive or restrictive interests and behaviors. ASD is known to have a significant genetic risk, but the underlying genetic variation can be attributed to hundreds of genes. The molecular and pathophysiologic basis of ASD remains elusive because of its genetic heterogeneity and complexity, its high comorbidity with other diseases, and the paucity of brain tissue for study. The invasive nature of collecting primary neuronal tissue from patients might be circumvented through reprogramming peripheral cells to induced pluripotent stem cells (iPSCs), which are able to generate live neurons carrying the genetic variants of disease. This breakthrough allows us to access the cellular and molecular phenotypes of patients with âintrinsic autismâ, that is patients without known genetic disorders or identifiable syndromes or malformations. To do this, we studied a relatively homogeneous patient population of boys with intrinsic autism by excluding patients with known genetic disease or recognizable phenotypes or syndromes, as well as those with profound mental retardation or primary seizure disorders. We generated iPSCs from patients with intrinsic autism, their unaffected male siblings and age-, and sex-matched unaffected controls. And these stem cells were subsequently differentiated into electrophysiologically active neurons. The expression profile for autistic and their unaffected siblings' iPSC-derived neurons were compared. A distinct expression profile was found between autism and sib control. The significantly differentially expressed genes (> 2-fold, FDR < 0.05) in autistic iPSC-derived neurons were significantly enriched for processes related to synaptic transmission, such as neuroactive ligand-receptor signaling and extracellular matrix interactions (FDR < 0.05), and were significantly enriched for genes previously associated with ASD (p < 0.05). Our findings suggest approaches such as iPSC-derived neurons will be an important method to obtain tissue for study that appropriately recapitulates the complex dynamics of an autistic neural cell. We generated induced pluripotent stem cells (iPSCs) from male patients with intrinsic autism, their unaffected male siblings, and age-, and sex-matched unaffected controls. And these stem cells were subsequently differentiated into electrophysiologically active neurons following 80 days of post-mitotic neural differentiation. These samples, including fibroblast, iPSC, iPSC-derived neural progenitors (NPC) and iPSC-derived neurons, were analyzed for the change of gene expression profile by whole genome microarray.
2016-07-01 | E-GEOD-65106 | biostudies-arrayexpress
Project description:Alterations in cortical neurogenesis are implicated in neurodevelopmental disorders including autism spectrum disorders (ASDs). Many ASD risk genes have been identified as critical for brain development, but the contribution of genetic backgrounds, although inferred in complex genetic disorders such as ASD, remains unclear. Here, using isogenic induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) and cortical organoid models, we report that a heterozygous PTEN p.I135L mutation found in an ASD patient with macrocephaly dysregulates cortical neurogenesis in an ASD genetic background-dependent fashion. We found that this PTEN p.I135L mutation led to overproduction of NPC subtypes as well as neuronal subtypes including both deep and upper layer neurons in its ASD background, but not when introduced into a control genetic background. ASD and control background differences in neurogenesis, neural development and synapse signaling were also observed. These findings provide experimental evidence that both a PTEN p.I135L mutation and ASD genetic background contribute to cellular features consistent with ASD associated with macrocephaly.
2023-03-20 | GSE221923 | GEO
Project description:Global gene expression analysis of FD-iPSC and deribved neural crest cells Here we report the derivation of patient specific Familial Dysautonomia-iPSCs and their directed differentiation into multiple cell types capable of modeling the tissue specific splicing defect in vitro. Undifferentiated hESCs were exposed to control and drug treatments for 24 hours followed by mRNA expression analysis Global gene expression analysis of FD-iPSC and derived neural crest cells
2009-08-31 | E-GEOD-17043 | biostudies-arrayexpress
Project description:Purpose: The goals of this study are to compare the transcriptomic profile (mRNA-seq) of HD and control patient iPSC-derived neural cells to identify alterations in gene expression Methods: RNA were isolated from HD and control iPSC-derived neural cells. mRNAseq using Illumina Truseq mRNA PolyA+ v2 lib prep and Hiseq 2000. Statistical difference in mRNA levels were calculated with subsequent GO and pathway analysis Results: mRNAseq and statistical analysis revealed 1869 differentially expressed genes between HD and control iPSC-derived neural cells. Conclusions: Our study shows 1869 differentially expressed genes between HD and control iPSC-derived neural cells, and reveals gene networks that relevant to the mechanism of HD pathogenesis.
2017-03-20 | GSE95343 | GEO
Project description:DNA methylation array of irradiated and/or lithium exposed iPSC-derived human neural progenitor cells
| PRJNA989243 | ENA