Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA153881 | 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:CNV analysis for Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations
| PRJNA153879 | 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:Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare, fatal premature aging disorder caused by a de novo mutation in the LMNA gene that leads to the production of progerin, a farnesylated, pathogenic form of lamin A. Treatment with farnesyltransferase inhibitors achieves significant yet limited life extension, highlighting progerin farnesylation as a key pathogenic driver of HGPS. In this study, rather than correcting the single pathogenic point mutation, we introduce Farnesylation Amino acid Targeted Editing (FATE), a novel, mutation-agnostic precision genome editing strategy that selectively disrupts the farnesylation site of LMNA. Next-generation sequencing confirmed that FATE exclusively edits the LMNA locus without inducing off-target mutations or affecting other genes encoding farnesylated proteins. Using neuromuscular organoids (NMOs) derived from two isogenic pairs of human pluripotent stem cells (hPSCs) carrying the HGPS mutation (HGPS-hPSCs), we found perinuclear progerin accumulation exclusive to the muscular compartment to be associated with defective formation of DNA damage foci and loss of perinuclear heterochromatin. Notably, applying FATE to HGPS-hPSCs successfully abolished these muscle-specific pathologies in subsequently-derived NMOs. Direct delivery of FATE mRNA into HGPS-NMOs likewise effectively inhibited perinuclear accumulation of progerin and rescued the formation of DNA damage repair foci. These findings demonstrate FATE as a broadly applicable, mutation-agnostic editing approach that targets a fundamental pathogenic mechanism in HGPS and therefore has feasible utility in clinical application.
2026-07-13 | GSE305237 | GEO
Project description:BACKGROUND: MYBPC3 is one of the most mutated gene known to cause hypertrophic cardiomyopathy (HCM). However, the molecular mechanisms of how mutations in MYBPC3 lead to the onset and progression of HCM are poorly understood. Thus, advancing in-vitro studies to define these mechanisms of mutations leading to HCM are still warranted. Thus, the primary objective of this study was to investigate the molecular mechanisms underlying the pathogenesis of HCM associated with MYBPC3 mutation utilizing isogenic human-induced pluripotent stem cell (hiPSC)-derived cardiac organoids (hCOs).
2025-01-28 | GSE262876 | GEO
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 enable advanced cognitive abilities, the human cortex undergoes complex developmental processes, disruption of which underlies neurodevelopmental disorders such as Schaaf-Yang syndrome (SYS) and Prader-Willi syndrome (PWS). While SYS is caused by pathogenic point mutations in the imprinted MAGEL2 gene, PWS arises from chromosomal deletions, imprinting defects or uniparental disomy encompassing the MAGEL2 locus. Here, bulk RNA-seq was performed on day-30 hiPSC-derived cortical neurons from two CRISPR/Cas9-engineered isogenic human pluripotent stem cell backgrounds (male GM08330 and female MGH2069) modeling MAGEL2-associated SYS and PWS variants, including WT, MAGEL2 c.1996dupC, MAGEL2 c.1996delC, heterozygous MAGEL2 deletion, homozygous MAGEL2 deletion, PWS type I deletion, and PWS type II deletion.
2026-08-21 | GSE329288 | GEO
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:Resistance against Verticillium longisporum is quantitative and multigenic. The vec1 QTL in Arabidopsis thaliana controlled resistance against systemic colonization by the fungus. Gene expression was studied to identify genes and pathways controlled by vec1. Near-isogenic lines derived from the resistant ecotype Bur and the susceptible ecotype Ler were compared. NIL9 contained Ler-alleles in the genomic region between 11753 and 12285 kb within vec1 on chromosome 2, tmNIL130 contained Bur-alleles. Microarrays were performed on samples containing the hypocotyl and the shoot basis because colonization is stopped in this region in resistant genotypes. Two developmental stages were studied: time-point (1) at the onset of flowering, when systemic colonization was shown to start and time point (2) at the onset of silique maturity, when extensive fungal proliferation was shown to occur. Two pathogen treatments were studied: (1) mock-inoculated controls, (2) plants inoculated with the V. longipsorum isolate 43 (VL).
2015-06-30 | GSE70021 | GEO