Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA153879 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE29772: CNV analysis for Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations GSE29773: Gene Expression Data for Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations Refer to individual Series
2011-07-25 | E-GEOD-29774 | biostudies-arrayexpress
Project description:Gene Expression Data for Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations
| PRJNA153881 | ENA
Project description:Parkinson disease (PD) is characterized by extensive loss of A9 dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). A strong association has been reported between PD and exposure to mitochondrial toxins such as the environmental pesticides paraquat, maneb, and rotenone. Here, using a robust, patient-derived, stem cell model of PD that allows comparison of -synuclein ( -syn) mutant cells and isogeneic mutation-corrected controls, we identify mitochondrial toxin-induced perturbations specific to A53T -syn mutant A9-DA neurons (hNs). We report a novel molecular pathway whereby basal as well as toxin-induced oxidative and nitrosative stress inhibits the MEF2C-PGC1 transcription network in A53T hNs compared to corrected controls, contributing to mitochondrial dysfunction and apoptotic cell death. Our data provide mechanistic insight into gene-environmental interaction (GxE) in the pathogenesis of PD. Furthermore, using small molecule high-throughput screening, we identify the MEF2C-PGC1 pathway as a new drug target for therapeutic benefit in PD. In the current study, isogenic hiPSCs differing exclusively at a single amino acid (A53T) were exposed to either 2.8uM paraquat in combination with 1uM maneb for 24h or PBS vehicle control. Gene expression profile was analysed to assess the effect of both the genotype and exposure regiment on gene expression.
2013-12-05 | E-GEOD-46798 | biostudies-arrayexpress
Project description:The 22q11.2 deletion syndrome (22q11.2DS) is the most common copy number variant (CNV)-associated syndrome, leading to congenital and neuropsychiatric anomalies. Patient-derived, induced pluripotent stem cell (iPS) models have provided important insight into the mechanisms of phenotypic features of this condition. However, patient-derived iPSC models may harbor underlying genetic heterogeneity that can confound analysis of pathogenic CNV effects. Furthermore, the ~1.5 Mb “A-B” deletion at this locus is inherited at higher frequency than the more common ~2.7 Mb “A-D” deletion, but remains under-studied due to lack of relevant models. To address these issues, here we leveraged a CRISPR-based strategy in Cas9-expressing iPS cells to engineer novel isogenic models of the 22q11.2 “A-B” deletion. After in vitro differentiation to excitatory neurons, integrated transcriptomic and cell surface proteomics identified deletion-associated alterations in surface adhesion markers. Furthermore, implantation of iPS-derived neuronal progenitor cells into the cortex of neonatal mice found decreased proliferation and accelerated neuronal maturation within a relevant microenvironment. Taken together, our results suggest potential pathogenic mechanisms of the 22q11.2 “A-B” deletion in driving neuronal and neurodevelopmental phenotypes. We further propose that the isogenic models generated here will provide a unique resource to study this less-common variant of the 22q11.2 microdeletion syndrome.
2023-05-11 | PXD032075 | Pride
Project description:Two soybean near-isogenic lines (NILs) differing in seed protein content were genotyped to determine differential genetic introgressions from the wild relative Glycine soja. The CGH comparison reveals loci that are differentially introgressed between the two lines.
2013-02-28 | GSE44725 | GEO
Project description:To probe into the molecular mechanism underlying the onset of choroidal neovascularization (CNV), integrated transcriptomic and proteomic analyses of the retinas in mice with laser-induced CNV were performed by using RNA sequencing and tandem mass tag.
2023-02-09 | PXD039971 |
Project description:To investigate gene expression changes related to two fAD mutations (A79V and L150P) in the Presenilin-1 gene (PSEN1) we compared the transcriptomes (polyA and total) of glutamatergic cortical neurons derived from fAD-mutant human induced pluripotent stem cells and their individual isogenic controls generated via precision CRISPR/Cas9 genome editing.
2023-01-24 | GSE211993 | GEO
Project description:Patient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells provide a unique tool for the study of human disease in disease relevant cells, as well as a promising source for cell replacement therapies for degenerative diseases. However one of the crucial limitations before realizing the full promise of this “disease in a dish” approach has been the inability to do controlled experiments under genetically defined conditions. This is particularly relevant for disorders with long latency periods, such as Parkinson’s disease (PD), where in vitro phenotypes of patient-derived iPSCs are predicted to be subtle and susceptible to significant epistatic effects of genetic background variations. By combining zinc-finger nuclease (ZFN)-mediated genome editing and iPSC technology we provide a generally applicable solution to this key problem by generating isogenic pairs of disease and control human embryonic stem cells (hESCs) and hiPSCs lines that differ exclusively at a susceptibility variant for PD by modifying a single point mutation (A53T) in the α-synuclein gene. The robust capability to genetically correct disease causing point mutations in patient-derived hiPSCs represents not only a significant progress for basic biomedical research but also a major advancement towards hiPSC-based cell replacement therapies using autologous cells. ZFN-mediated genome edited human iPS cells or ES cells were assayed for gene expression
2011-07-25 | E-GEOD-29773 | biostudies-arrayexpress
Project description:Patient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells provide a unique tool for the study of human disease in disease relevant cells, as well as a promising source for cell replacement therapies for degenerative diseases. However one of the crucial limitations before realizing the full promise of this “disease in a dish” approach has been the inability to do controlled experiments under genetically defined conditions. This is particularly relevant for disorders with long latency periods, such as Parkinson’s disease (PD), where in vitro phenotypes of patient-derived iPSCs are predicted to be subtle and susceptible to significant epistatic effects of genetic background variations. By combining zinc-finger nuclease (ZFN)-mediated genome editing and iPSC technology we provide a generally applicable solution to this key problem by generating isogenic pairs of disease and control human embryonic stem cells (hESCs) and hiPSCs lines that differ exclusively at a susceptibility variant for PD by modifying a single point mutation (A53T) in the ?-synuclein gene. The robust capability to genetically correct disease causing point mutations in patient-derived hiPSCs represents not only a significant progress for basic biomedical research but also a major advancement towards hiPSC-based cell replacement therapies using autologous cells. ZFN-mediated genome edited human iPS cells or ES cells were assayed for genomic variation
2011-07-25 | E-GEOD-29772 | biostudies-arrayexpress