Molecular pathway analysis towards understanding tissue vulnerability in spinocerebellar ataxia type 1
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA503578 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptome analysis of extracted total RNA from the the cerebellum and muscle of Spinocerebellar Ataxia 17 knock-in mouse model
2015-08-19 | GSE72176 | GEO
Project description:Vulnerability of Purkinje cells induced from spinocerebellar ataxia type 6 patient-derived iPS cells
| PRJNA338237 | ENA
Project description:Purpose: The goals of this study were to identify the molecular alterations in the SCA1 inferior olive, and determine whether these changes are found in other affected tissues. Methods: mRNA profiling was conducted in two different SCA1 mouse models (Atxn1 154Q/2Q KI and ATXN1-82Q Tg), in two different affected tisues (inferior olive and cerebellum) during early disease initiation and progression (5 week and 12 week time-points). All analyses were conducted relative to appropriate wild-type controls. TopHat2 v2.1.0 was utilized to align reads to the mouse reference genome (mm10) before quantification and differential expression analysis with Cufflinks v2.2.1. Normalized expression values were generated using Cuffnorm. Results: Differentially regulated genes identified in the SCA1 inferior olive segregated into several enriched biological pathways, including the Defense Response at 12 weeks of age. Our study demonstrates that vulnerable tissues in SCA1 are not uniform in their gene expression changes, and express discrete and commonly enriched biological pathways. In addition, we found that brain region-specific differences occur early in disease initiation and progression at 5 weeks of age. Conclusions: The findings from this study suggest that different mechanisms of neurodegeneration are at work in the SCA1 inferior olive and cerebellum.
2018-12-04 | GSE122099 | GEO
Project description:The neurodegenerative disorder spinocerebellar ataxia type 1 (SCA1) affects the cerebellum and inferior olive, though previous research has focused primarily on the cerebellum. As a result, it is unknown what molecular alterations are present in the inferior olive, and whether these changes are found in other affected tissues. This study addresses these questions for the first time using two different SCA1 mouse models. We found that differentially regulated genes in the inferior olive segregated into several biological pathways. Comparison of the inferior olive and cerebellum demonstrates that vulnerable tissues in SCA1 are not uniform in their gene expression changes, and express largely discrete but some commonly enriched biological pathways. Importantly, we also found that brain-region-specific differences occur early in disease initiation and progression, and they are shared across the two mouse models of SCA1. This suggests different mechanisms of degeneration at work in the inferior olive and cerebellum.
| S-EPMC6292693 | biostudies-literature
Project description:Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by loss of Purkinje cells in the cerebellum. SCA6 is caused by CAG trinucleotide repeat expansion in CACNA1A, which encodes Cav2.1, ?1A subunit of P/Q-type calcium channel. However, the pathogenic mechanism and effective therapeutic treatments are still unknown. Here we have succeeded in generation of differentiated Purkinje cells that carry the patient genes by combining disease-specific iPS cells and self-organizing culture technologies. SCA6-iPS cells derived Purkinje cells exhibited increased level of whole Cav2.1 protein while decreased level of its C-terminal fragment and downregulation of the transcriptional targets TAF1 and BTG1. We further demonstrate that SCA6-Purkinje cells exhibit thyroid hormone depletion-dependent degeneration, which can be suppressed by two compounds, thyroid releasing hormone and Riluzole. Thus we have constructed an in vitro disease model recapitulating both ontogenesis and pathogenesis. This model would be useful for pathogenic investigation and drug screening. Examination of mRNA profile in 1 ES cell line, two healthy donnor-derived iPS cell lines, three case-derived iPS cell lines and 1 normal dermal fibroblasts.
2016-11-08 | E-GEOD-85347 | biostudies-arrayexpress
Project description:Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by loss of Purkinje cells in the cerebellum. It is known to be caused by CAG trinucleotide repeat expansion in CACNA1A, the gene that encodes Cav2.1, α1A subunit of P/Q-type calcium channel. However, the pathogenic mechanism and effective therapeutic treatments are still unknown. Here we have succeeded in generation of mature Purkinje cells that carry the patient genes by combining patient-derived iPS cell and self-organizing culture technologies. Patient-derived Purkinje cells exhibited upregulation of whole Cav2.1 protein while downregulation of its C-terminal fragment and the transcriptional targets TAF1 and BTG1. We further demonstrate that patient Purkinje cells exhibit thyroid hormone depletion-dependent degeneration, which can be suppressed by two compounds, thyroid releasing hormone and Riluzole. Thus we have constructed an in vitro disease model recapitulating both ontogenesis and pathogenesis. This model would be useful for pathogenic investigation and drug screening
2016-11-08 | GSE85348 | GEO
Project description:Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by loss of Purkinje cells in the cerebellum. SCA6 is caused by CAG trinucleotide repeat expansion in CACNA1A, which encodes Cav2.1, α1A subunit of P/Q-type calcium channel. However, the pathogenic mechanism and effective therapeutic treatments are still unknown. Here we have succeeded in generation of differentiated Purkinje cells that carry the patient genes by combining disease-specific iPS cells and self-organizing culture technologies. SCA6-iPS cells derived Purkinje cells exhibited increased level of whole Cav2.1 protein while decreased level of its C-terminal fragment and downregulation of the transcriptional targets TAF1 and BTG1. We further demonstrate that SCA6-Purkinje cells exhibit thyroid hormone depletion-dependent degeneration, which can be suppressed by two compounds, thyroid releasing hormone and Riluzole. Thus we have constructed an in vitro disease model recapitulating both ontogenesis and pathogenesis. This model would be useful for pathogenic investigation and drug screening.
2016-11-08 | GSE85347 | GEO
Project description:Towards a Genomic Understanding of Myeloma
| PRJNA75317 | ENA
Project description:Transcriptomic approach reveals splicing dysregulation in spinocerebellar ataxia type 1
| PRJNA971864 | ENA
Project description:Spinocerebellar ataxia type 2 (SCA2) is among the progressive neurodegenerative polyglutamine (polyQ) diseases. It is caused by a CAG repeat expansion in an encoded region of the ATXN2 gene giving rise to an expanded polyQ domain in the encoded ATXN2 protein. SCA2 is an autosomal dominant disorder characterized by symptoms resulting from neurodegeneration of cerebellar Purkinje cells. To molecularly characterize SCA2 disease progression, we analyzed RNA-sequencing data produced using the cerebella of ATXN2Q127 mice collected at three distinct time points. The ATXN2Q127 mouse model contains 127 CAG repeats in the full-length ATXN2 cDNA under the control of the PC targeted Pcp2 promoter.
2017-12-09 | E-MTAB-6293 | biostudies-arrayexpress