Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA264804 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Brain gene transfer using viral vectors will likely become a therapeutic option for several disorders. Helper-dependent (HD) canine adenovirus type 2 vectors (CAV-2) are well suited for this goal. Indeed, these vectors are poorly immunogenic, efficiently transduce neurons, are retrogradely transported to afferent structures in the brain, and lead to long-term transgene expression. CAV-2 vectors have been exploited to unravel behavior, cognition, neural networks, axonal transport and therapy for orphan diseases. Here we describe the HD-CAV-2 vector induced transcriptional response of human dopaminergic neurospheres derived from midbrain progenitors. In this 3D model system, brain cell functions and dynamics mimic several aspects the dynamic nature of human brain. With the goal of better understanding and characterizing HD CAV-2 for brain therapy, we analyzed the transcriptomic modulation induced by HD-CAV-2 in this brain model system. We found that dopaminergic neurospheres are readily transduced by HD-CAV-2, and that transduction generates two main responses: a DNA damage response, and alteration of centromeric and microtubule probes. We suggest that the first effect is linked to viral DNA, while the second would be related to the interaction of the HD-CAV-2 fibre with CAR. Total RNAs extracted from 3D cultures of transduced hmNPCs cells at 2 h and 5 days post-infection with HD-CAV-2 vector were hybridized on Affymetrix microarrays and pair wise comparisons were performed between the mock and vector transduced hmNPCs cells. Each condition was tested in three replicates.
2014-10-24 | E-GEOD-62687 | biostudies-arrayexpress
Project description:Vector-transduced neurons transcriptome profiles
| PRJNA203697 | ENA
Project description:Brain gene transfer using viral vectors will likely become a therapeutic option for several disorders. Helper-dependent (HD) canine adenovirus type 2 vectors (CAV-2) are well suited for this goal. Indeed, these vectors are poorly immunogenic, efficiently transduce neurons, are retrogradely transported to afferent structures in the brain, and lead to long-term transgene expression. CAV-2 vectors have been exploited to unravel behavior, cognition, neural networks, axonal transport and therapy for orphan diseases. Here we describe the HD-CAV-2 vector induced transcriptional response of human dopaminergic neurospheres derived from midbrain progenitors. In this 3D model system, brain cell functions and dynamics mimic several aspects the dynamic nature of human brain. With the goal of better understanding and characterizing HD CAV-2 for brain therapy, we analyzed the transcriptomic modulation induced by HD-CAV-2 in this brain model system. We found that dopaminergic neurospheres are readily transduced by HD-CAV-2, and that transduction generates two main responses: a DNA damage response, and alteration of centromeric and microtubule probes. We suggest that the first effect is linked to viral DNA, while the second would be related to the interaction of the HD-CAV-2 fibre with CAR.
2014-10-24 | GSE62687 | GEO
Project description:With the goal of specifically dissecting the toxicogenomic signatures of the helper-dependent (HD) human (HAd5) and canine (CAV-2) adenovirus, the VSV-G-pseudotyped SIN HIV-1 (LV) and the Adenoviral-associated vector 2/9 for human neurons (AAV2/9), we transduced a bona fide human neuronal system with HD-HAd5, HD-CAV-2, LV and AAV2/9, we analysed the transcriptional response of more than 47,000 transcripts using gene chips. Chip data showed that HD-CAV-2 and LV vectors both activated the innate arm of the immune response, including Toll-like receptors and hyaluronan circuits. LV vector induced as well an IFN response. Moreover, HD-CAV-2 and LV vectors affected DNA damage pathways - at 5 days in opposite directions - suggesting a differential response of the p53 and ATM pathways to the vector genomes. As a general response to the vectors, human neurons activated pro-survival genes and neuron morphogenesis. Total RNAs extracted from transduced hmNPCs cells at 2 h and 5 days post-infection with HD-HAd, HD-CAV-2, LV and AAV2/9 vectors were hybridizated on Affymetrix microarrays and paired pair wise comparisons were performed between the mock and vector transduced hmNPCs cells. Each condition was tested in three replicates.
2013-05-22 | E-GEOD-47130 | biostudies-arrayexpress
Project description:With the goal of specifically dissecting the toxicogenomic signatures of the helper-dependent (HD) human (HAd5) and canine (CAV-2) adenovirus, the VSV-G-pseudotyped SIN HIV-1 (LV) and the Adenoviral-associated vector 2/9 for human neurons (AAV2/9), we transduced a bona fide human neuronal system with HD-HAd5, HD-CAV-2, LV and AAV2/9, we analysed the transcriptional response of more than 47,000 transcripts using gene chips. Chip data showed that HD-CAV-2 and LV vectors both activated the innate arm of the immune response, including Toll-like receptors and hyaluronan circuits. LV vector induced as well an IFN response. Moreover, HD-CAV-2 and LV vectors affected DNA damage pathways - at 5 days in opposite directions - suggesting a differential response of the p53 and ATM pathways to the vector genomes. As a general response to the vectors, human neurons activated pro-survival genes and neuron morphogenesis.
2013-05-22 | GSE47130 | GEO
Project description:Neural stem/progenitor cells were isolated from the lateral ventricle wall of 4-6 week-old CD1 mice and grown as neurospheres under low density culture conditions. Test cells were transduced with bicistronic retroviral constructs for the over-expression of Bmi1 together with eGFP, and control cells were transduced with an empty vector construct expressing eGFP only. To identify genes, which are regulated by BMI1 in neural stem/progenitor cells, the gene expression profiles of neurosphere cells over-expressing Bmi1 were compared empty vector control cells using Affymetrix Gene mouse ST1.0 arrays
2016-06-01 | GSE70451 | GEO
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:Single-nucleus RNA sequencing (snRNA-seq) was used to profile the transcriptome of 16,015 nuclei in human adult testis. This dataset includes five samples from two different individuals. This dataset is part of a larger evolutionary study of adult testis at the single-nucleus level (97,521 single-nuclei in total) across mammals including 10 representatives of the three main mammalian lineages: human, chimpanzee, bonobo, gorilla, gibbon, rhesus macaque, marmoset, mouse (placental mammals); grey short-tailed opossum (marsupials); and platypus (egg-laying monotremes). Corresponding data were generated for a bird (red junglefowl, the progenitor of domestic chicken), to be used as an evolutionary outgroup.
2021-11-08 | E-MTAB-11063 | biostudies-arrayexpress