Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA174513 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR557149.fastq.gz | Fastqsanger.gz | |||
| SRR557149_1.fastq.gz | Fastqsanger.gz | |||
| SRR557149_2.fastq.gz | Fastqsanger.gz | |||
| SRR557150.fastq.gz | Fastqsanger.gz | |||
| SRR557150_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
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Project description:Allele-Preferred Targeted Correction of CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells
| PRJNA174436 | ENA
Project description:Production of functional proteins requires multiple steps including gene transcription and post-translational processing. MicroRNAs (miRNA) can regulate individual stages of these processes. Despite the importance of the cystic fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion transport, how its expression is regulated remains uncertain. We discovered that microRNA-138 regulates CFTR expression through its interactions with the transcriptional regulatory protein SIN3A. Treating airway epithelia with a miR-138 mimic increased CFTR mRNA and also enhanced CFTR abundance and transepithelial Cl- permeability independently of elevated mRNA levels. A miR-138 anti-miR had the opposite effects. Importantly, miR-138 altered the expression of many genes encoding proteins that associate with CFTR and may influence its biosynthesis. The most common CFTR mutation, M-NM-^TF508, causes protein misfolding, degradation, and cystic fibrosis. Remarkably, manipulating the miR-138 regulatory network also improved biosynthesis of CFTR-M-NM-^TF508 and restored Cl- transport to cystic fibrosis airway epithelia. This novel miRNA-regulated network directs gene expression from the chromosome to the cell membrane, indicating that an individual miRNA can control a cellular process broader than previously recognized. This discovery also provides new therapeutic avenues for restoring CFTR function to cells affected by the most common cystic fibrosis mutation. 12 samples of Calu-3 cells representing different interventions.
2012-09-04 | E-GEOD-38956 | biostudies-arrayexpress
Project description:Organotypic culture systems from disease-specific induced pluripotent stem cells (iPSCs) exhibit obvious advantages compared to immortalized cell lines and primary cell cultures but implementation of iPSC-based high throughput (HT) assays is still technically challenging. Here we demonstrate the development and conduction of an organotypic HT Cl-/I- exchange assay using Cystic Fibrosis (CF) disease-specific iPSCs. The introduction of a halide sensitive YFP variant enabled automated quantitative measurement of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function in iPSC-derived intestinal epithelia. CFTR function was partially rescued by treatment with VX-770 and VX-809, and seamless gene correction of the p.Phe508del mutation resulted in full restoration of CFTR function. The identification of a series of validated primary hits that improve the function of p.Phe508del CFTR from a library of ~ 42.500 chemical compounds demonstrates that the advantages of complex iPSC-derived culture systems for disease modelling can also be utilized for drug screening at a true HT format.
2019-05-11 | GSE129168 | GEO
Project description:The purpose of this study was to explore baseline expression of miRNome in Cystic Fibrosis Bronchial Epithelial (CFBE41o-) cells stably transfected with wild type (WT) Cystic Fibrosis Transmembrane Conductance regulator (CFTR) and F508del-CFTR. To fulfill this goal miRNA sequencing was done to see miRNA landscape in CFBE41o- Cells with homozygous F508del mutated CFTR and in CFBE41o- Cells with homozygous WT-CFTR, without any treatment condition.
2019-03-28 | GSE128912 | GEO
Project description:The purpose of this study was to explore miRNA mediated Transforming Growth Factor (TGF)-β1 regulation of F508del Cystic Fibrosis Transmembrane Conductance regulator (CFTR). To fulfill this goal, miRNA sequencing was done to see miRNA landscape in Cystic Fibrosis Bronchial Epithelial (CFBE) Cells with homozygous WT-CFTR and F508del mutated CFTR in response to TGFβ1 treatment.
2019-03-25 | GSE128765 | GEO
Project description:The occurrence of attention deficit-hyperactivity disorder (ADHD) symptoms in patients with cystic fibrosis (CF) is substantially higher than in the general population, and the cystic fibrosis transmembrane conductance regulator (CFTR) is the pathogenic gene of cystic fibrosis, suggesting the potentially critical role of CFTR in ADHD. Here, we identified three heterozygous missense mutations (p.E217G, p.F316L and p.T1220I) in CFTR, segregating with ADHD in two consanguineous families with 6 affected individuals. Using the zebrafish model, we found that the cftr knockout line displays hyperactive, impulsive-like, and attention deficit-like behaviors, reminiscent of human ADHD patients. Single-cell RNA-seq of 7 dpf larvae identified clusters of neuron cells that were sensitive to cftr, especially, the number of dopaminergic neuron cells decreased in the cftr mutant fish. Bulk RNA-seq and proteomic analysis at the early gastrulation period showed that the expression of nerve system genes was abnormal. Notably, we tried to use CFTR activitors Lumacaftor (VX-809) and Ivacaftor (VX-770) to treat the ADHD zebrafish model (established by per1b mutant), and found enhanced CFTR activity could rescue the ADHD-like behaviors. In brief, we uncover the role of CFTR in ADHD pathogenesis and explore novel diagnoses and therapy for ADHD by targeting CFTR.
2024-12-16 | GSE284214 | GEO
Project description:Cystic fibrosis (CF) is one of the most prevalent lethal genetic diseases with over 2000 identified genetic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Pharmacological chaperones such as Lumacaftor (VX-809), Tezacaftor (VX-661) and Elexacaftor (VX-445) treat mutation-induced defects by stabilizing CFTR and are called correctors. These correctors improve proper folding and thus facilitate processing and trafficking to increase the amount of functional CFTR on the cell surface. Yet, CFTR variants display differential responses to each corrector. Here, we report variants P67L and L206W respond similarly to VX-809 but divergently to VX-445 with P67L exhibiting little rescue when treated with VX-445. We investigate the underlying cellular mechanisms of how CFTR biogenesis is altered by correctors in these variants. Affinity purification-mass spectrometry (AP-MS) multiplexed with isobaric Tandem Mass Tags (TMT) was used to quantify CFTR protein-protein interaction changes between variants P67L and L206W. VX-445 facilitates unique proteostasis factor interactions especially in translation, folding, and degradation pathways in a CFTR variant-dependent manner. A number of these interacting proteins knocked down by siRNA, such as ribosomal subunit proteins, moderately rescued fully glycosylated P67L. Importantly, these knock-downs sensitize P67L to VX-445 and further enhance the correction of this variant. Our results provide a better understanding of VX-445 biological mechanism of action and reveal cellular targets that may sensitize unresponsive CFTR variants to known and available correctors.
2023-09-18 | PXD039773 | Pride
Project description:Production of functional proteins requires multiple steps including gene transcription and post-translational processing. MicroRNAs (miRNA) can regulate individual stages of these processes. Despite the importance of the cystic fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion transport, how its expression is regulated remains uncertain. We discovered that microRNA-138 regulates CFTR expression through its interactions with the transcriptional regulatory protein SIN3A. Treating airway epithelia with a miR-138 mimic increased CFTR mRNA and also enhanced CFTR abundance and transepithelial Cl- permeability independently of elevated mRNA levels. A miR-138 anti-miR had the opposite effects. Importantly, miR-138 altered the expression of many genes encoding proteins that associate with CFTR and may influence its biosynthesis. The most common CFTR mutation, ΔF508, causes protein misfolding, degradation, and cystic fibrosis. Remarkably, manipulating the miR-138 regulatory network also improved biosynthesis of CFTR-ΔF508 and restored Cl- transport to cystic fibrosis airway epithelia. This novel miRNA-regulated network directs gene expression from the chromosome to the cell membrane, indicating that an individual miRNA can control a cellular process broader than previously recognized. This discovery also provides new therapeutic avenues for restoring CFTR function to cells affected by the most common cystic fibrosis mutation.
2012-09-04 | GSE38956 | GEO
Project description:Cystic fibrosis bronchial epithelial (CFBE41o-ΔF508) cells subjected to 23 bio-active small molecules including vehicle controls, at low temperature and untreated cells. Untreated Cystic fibrosis bronchial epithelial cells (CFBE41o−CFTR) are also included.
2016-12-12 | GSE67698 | GEO
Project description:Airways conduct gases to the lung and are disease sites of asthma and cystic fibrosis. Here we study the cellular composition and hierarchy of the mouse tracheal epithelium by single-cell RNA-sequencing (scRNA-seq) and in vivo lineage tracing. We identify a rare cell type, the Foxi1+ pulmonary ionocyte; functional variations in club cells by proximodistal location; a distinct cell type in high turnover squamous epithelial structures that we term 'hillocks'; and disease-relevant subsets of tuft and goblet cells. We developed 'pulse-seq' , combining scRNA-seq and lineage tracing, to show that tuft, neuroendocrine and ionocyte cells are continually and directly replenished by basal progenitor cells. Ionocytes are the major source of transcripts of the cystic fibrosis transmembrane conductance regulator in both mouse (Cftr) and human (CFTR). Knockout of Foxi1 in mouse ionocytes causes loss of Cftr expression and disrupts airway fluid and mucus physiology, phenotypes that characterize cystic fibrosis. By associating cell-type-specific expression programs with key disease genes, we establish a new cellular narrative for airways disease.
2018-07-30 | GSE103354 | GEO