Genes induced by Oxi-beta overexpression in dopaminergic neuronal cell SN4741
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE47634 | GEO | 2013/06/05
SECONDARY ACCESSION(S): PRJNA206967
REPOSITORIES: GEO
Similar Datasets
Project description:To identify genes regulated by Oxi-beta, differential gene chip analysis was perfomed. And the greatest upregulation (about 25-fold) of FBXW5 mRNA was observed in response to Oxi-beta overexpression in SN4741 dopaminergic neuronal cells Total RNAs obtained from subjected to overexpression of Oxi-beta for 12 hours compared to control SN4741 cells at 0 hr.
2013-06-05 | E-GEOD-47634 | biostudies-arrayexpress
Project description:To overcome the ethical and technical limitations of in vivo human disease models, the broader scientific community frequently employs model organism-derived cell lines to investigate of disease mechanisms, pathways, and therapeutic strategies. Despite the widespread use of certain in vitro models, many still lack contemporary genomic analysis supporting their use as a proxy for the affected human cells and tissues. Consequently, it is imperative to determine how accurately and effectively any proposed biological surrogate may reflect the biological processes it is assumed to model. One such cellular surrogate of human disease is the established mouse neural precursor cell line, SN4741, which has been used to elucidate mechanisms of neurotoxicity in Parkinson disease for over 25 years. Here, we are using a combination of classic and contemporary genomic techniques – karyotyping, RT-qPCR, single cell RNA-seq, bulk RNA-seq, and ATAC-seq – to characterize the transcriptional landscape, chromatin landscape, and genomic architecture of this cell line, and evaluate its suitability as a proxy for midbrain dopaminergic neurons in the study of Parkinson disease. We find that SN4741 cells possess an unstable triploidy and consistently exhibits low expression of dopaminergic neuron markers across assays, even when the cell line is shifted to the non-permissive temperature that drives differentiation. The transcriptional signatures of SN4741 cells suggest that they are maintained in an undifferentiated state at the permissive temperature and differentiate into immature neurons at the non-permissive temperature; however, they may not be dopaminergic neuron precursors, as previously suggested. Additionally, the chromatin landscapes of SN4741 cells, in both the differentiated and undifferentiated states, are not concordant with the open chromatin profiles of ex vivo, mouse E15.5 forebrain- or midbrain-derived dopaminergic neurons. Overall, our data suggest that SN4741 cells may reflect early aspects of neuronal differentiation but are likely not a suitable a proxy for dopaminergic neurons as previously thought. The implications of this study extend broadly, illuminating the need for robust biological and genomic rationale underpinning the use of in vitro models of molecular processes.
2023-02-13 | GSE225082 | GEO
Project description:To overcome the ethical and technical limitations of in vivo human disease models, the broader scientific community frequently employs model organism-derived cell lines to investigate of disease mechanisms, pathways, and therapeutic strategies. Despite the widespread use of certain in vitro models, many still lack contemporary genomic analysis supporting their use as a proxy for the affected human cells and tissues. Consequently, it is imperative to determine how accurately and effectively any proposed biological surrogate may reflect the biological processes it is assumed to model. One such cellular surrogate of human disease is the established mouse neural precursor cell line, SN4741, which has been used to elucidate mechanisms of neurotoxicity in Parkinson disease for over 25 years. Here, we are using a combination of classic and contemporary genomic techniques – karyotyping, RT-qPCR, single cell RNA-seq, bulk RNA-seq, and ATAC-seq – to characterize the transcriptional landscape, chromatin landscape, and genomic architecture of this cell line, and evaluate its suitability as a proxy for midbrain dopaminergic neurons in the study of Parkinson disease. We find that SN4741 cells possess an unstable triploidy and consistently exhibits low expression of dopaminergic neuron markers across assays, even when the cell line is shifted to the non-permissive temperature that drives differentiation. The transcriptional signatures of SN4741 cells suggest that they are maintained in an undifferentiated state at the permissive temperature and differentiate into immature neurons at the non-permissive temperature; however, they may not be dopaminergic neuron precursors, as previously suggested. Additionally, the chromatin landscapes of SN4741 cells, in both the differentiated and undifferentiated states, are not concordant with the open chromatin profiles of ex vivo, mouse E15.5 forebrain- or midbrain-derived dopaminergic neurons. Overall, our data suggest that SN4741 cells may reflect early aspects of neuronal differentiation but are likely not a suitable a proxy for dopaminergic neurons as previously thought. The implications of this study extend broadly, illuminating the need for robust biological and genomic rationale underpinning the use of in vitro models of molecular processes.
2023-02-13 | GSE225076 | GEO
Project description:To overcome the ethical and technical limitations of in vivo human disease models, the broader scientific community frequently employs model organism-derived cell lines to investigate of disease mechanisms, pathways, and therapeutic strategies. Despite the widespread use of certain in vitro models, many still lack contemporary genomic analysis supporting their use as a proxy for the affected human cells and tissues. Consequently, it is imperative to determine how accurately and effectively any proposed biological surrogate may reflect the biological processes it is assumed to model. One such cellular surrogate of human disease is the established mouse neural precursor cell line, SN4741, which has been used to elucidate mechanisms of neurotoxicity in Parkinson disease for over 25 years. Here, we are using a combination of classic and contemporary genomic techniques – karyotyping, RT-qPCR, single cell RNA-seq, bulk RNA-seq, and ATAC-seq – to characterize the transcriptional landscape, chromatin landscape, and genomic architecture of this cell line, and evaluate its suitability as a proxy for midbrain dopaminergic neurons in the study of Parkinson disease. We find that SN4741 cells possess an unstable triploidy and consistently exhibits low expression of dopaminergic neuron markers across assays, even when the cell line is shifted to the non-permissive temperature that drives differentiation. The transcriptional signatures of SN4741 cells suggest that they are maintained in an undifferentiated state at the permissive temperature and differentiate into immature neurons at the non-permissive temperature; however, they may not be dopaminergic neuron precursors, as previously suggested. Additionally, the chromatin landscapes of SN4741 cells, in both the differentiated and undifferentiated states, are not concordant with the open chromatin profiles of ex vivo, mouse E15.5 forebrain- or midbrain-derived dopaminergic neurons. Overall, our data suggest that SN4741 cells may reflect early aspects of neuronal differentiation but are likely not a suitable a proxy for dopaminergic neurons as previously thought. The implications of this study extend broadly, illuminating the need for robust biological and genomic rationale underpinning the use of in vitro models of molecular processes.
2023-02-13 | GSE225069 | GEO
Project description:To overcome the ethical and technical limitations of in vivo human disease models, the broader scientific community frequently employs model organism-derived cell lines to investigate of disease mechanisms, pathways, and therapeutic strategies. Despite the widespread use of certain in vitro models, many still lack contemporary genomic analysis supporting their use as a proxy for the affected human cells and tissues. Consequently, it is imperative to determine how accurately and effectively any proposed biological surrogate may reflect the biological processes it is assumed to model. One such cellular surrogate of human disease is the established mouse neural precursor cell line, SN4741, which has been used to elucidate mechanisms of neurotoxicity in Parkinson disease for over 25 years. Here, we are using a combination of classic and contemporary genomic techniques – karyotyping, RT-qPCR, single cell RNA-seq, bulk RNA-seq, and ATAC-seq – to characterize the transcriptional landscape, chromatin landscape, and genomic architecture of this cell line, and evaluate its suitability as a proxy for midbrain dopaminergic neurons in the study of Parkinson disease. We find that SN4741 cells possess an unstable triploidy and consistently exhibits low expression of dopaminergic neuron markers across assays, even when the cell line is shifted to the non-permissive temperature that drives differentiation. The transcriptional signatures of SN4741 cells suggest that they are maintained in an undifferentiated state at the permissive temperature and differentiate into immature neurons at the non-permissive temperature; however, they may not be dopaminergic neuron precursors, as previously suggested. Additionally, the chromatin landscapes of SN4741 cells, in both the differentiated and undifferentiated states, are not concordant with the open chromatin profiles of ex vivo, mouse E15.5 forebrain- or midbrain-derived dopaminergic neurons. Overall, our data suggest that SN4741 cells may reflect early aspects of neuronal differentiation but are likely not a suitable a proxy for dopaminergic neurons as previously thought. The implications of this study extend broadly, illuminating the need for robust biological and genomic rationale underpinning the use of in vitro models of molecular processes.
2023-02-13 | GSE225071 | GEO
Project description:Genes induced by Oxi-beta overexpression in dopaminergic neuronal cell SN4741
| PRJNA206967 | ENA
Project description:We investigated mechanisms by which LXRs regulate midbrain dopaminergic neuron development. Using a systems biology approach, we found that LXR interacts with β-catenin and that LXR activation inhibits the activity of the Wnt/β-catenin pathway
2020-05-05 | GSE66118 | GEO
Project description:Circadian rhythm dysfunction is a hallmark of Parkinson Disease (PD), and diminished expression of the core clock gene Bmal1 has been described in PD patients. BMAL1 is required for core circadian clock function, but also serves non-rhythmic functions. Germline Bmal1 deletion can cause brain oxidative stress and synapse loss in mice, and can exacerbate dopaminergic neurodegeneration in response to MPTP. Here we examined the impact of cell type-specific Bmal1 deletion on dopaminergic neuron viability in vivo. We observed that global, post-natal deletion of Bmal1 caused spontaneous loss of tyrosine hydroxylase-positive (TH+) dopaminergic neurons in the substantia nigra pars compacta (SNpc). This was not due to disruption of behavioral circadian rhythms, and was not induced by astrocyte- or microglia-specific Bmal1 deletion. However, either pan-neuronal or TH neuron-specific Bmal1 deletion caused cell-autonomous loss of TH+ neurons in the SNpc. Finally, global Bmal1 deletion exacerbated TH+ neuron loss following injection of alpha-synclein fibrils. Transcriptomic analysis of neuron-specific Bmal1 KO brain revealed dysregulation of pathways involved in oxidative phosphorylation and Parkinson Disease.
2023-08-18 | GSE241200 | GEO
Project description:Personalized cell therapy is being explored as promising treatments for incurable diseases such as Parkinson’s disease (PD). Here, we directly reprogrammed human fibroblasts into induced dopaminergic neuronal progenitors (hiDPs) and assess their applicability for regenerative PD therapy. We found that hiDPs maintain progenitor characteristics over 20 passages and showed unaltered differentiation potential to midbrain dopaminergic neurons. By next-generation sequencing, we confirm that even long-term cultured hiDPs retain genomic stability, resulting in absence of tumorigenicity when transplanted, indicating preclinical safety. The hiDPs differentiate into highly pure dopaminergic neurons expressing markers associated with positive graft outcomes without unwanted serotonergic neurons known to cause graft-induced dyskinesia. The therapeutic effect and safety were confirmed by transplantation in rodent PD models. Because our optimized reprogramming conditions generate highly expandable hiDPs enabling scaled production of clonal cells and overcoming quality control issues, we propose that our hiDPs can become a preferred autologous therapy for aged and feeble PD patients vulnerable to immunosuppression regimens.
2023-08-31 | GSE157392 | GEO
Project description:Personalized cell therapy is being explored as promising treatments for incurable diseases such as Parkinson’s disease (PD). Here, we directly reprogrammed human fibroblasts into induced dopaminergic neuronal progenitors (hiDPs) and assess their applicability for regenerative PD therapy. We found that hiDPs maintain progenitor characteristics over 20 passages and showed unaltered differentiation potential to midbrain dopaminergic neurons. By next-generation sequencing, we confirm that even long-term cultured hiDPs retain genomic stability, resulting in absence of tumorigenicity when transplanted, indicating preclinical safety. The hiDPs differentiate into highly pure dopaminergic neurons expressing markers associated with positive graft outcomes without unwanted serotonergic neurons known to cause graft-induced dyskinesia. The therapeutic effect and safety were confirmed by transplantation in rodent PD models. Because our optimized reprogramming conditions generate highly expandable hiDPs enabling scaled production of clonal cells and overcoming quality control issues, we propose that our hiDPs can become a preferred autologous therapy for aged and feeble PD patients vulnerable to immunosuppression regimens.
2023-08-31 | GSE157340 | GEO