Vimentin network dysregulation mediates neurite deficits in SNCA duplication 2 Parkinson’s patient-derived midbrain neurons [RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1256454 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33341762.fastq.gz | Fastqsanger.gz | |||
| SRR33341763.fastq.gz | Fastqsanger.gz | |||
| SRR33341764.fastq.gz | Fastqsanger.gz | |||
| SRR33341765.fastq.gz | Fastqsanger.gz | |||
| SRR33341766.fastq.gz | Fastqsanger.gz |
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Project description:Duplication of the SNCA gene (SNCADupl), linked to elevated levels of alpha-synuclein (aSyn), is a genetic cause of Parkinson's disease (PD). Our prior work with human-induced pluripotent stem cell (hiPSC)-derived midbrain neurons generated from PD SNCADupl patients identified neuritic deficits, accompanied by decreased levels of cytoskeletal element b-tubulin-III (bTubIII). To explore mechanisms underlying these effects in SNCADupl neurons, we employed CRISPR/Cas9 to generate isogenic control hiPSCs. Isogenic correction of SNCA dosage restored SNCADupl-induced neurite defects and bTubIII levels. Multi-omics analyses revealed SNCADupl-induced alterations in neuronal differentiation, with a notable downregulation of PAX6. Moreover, SNCADupl induced an upregulation of vimentin. Further characterization revealed heightened vimentin truncation, associated with altered distribution and organization. Similar changes in vimentin levels and truncation were observed in post-mortem putamen tissue from sporadic PD patients. Notably, targeting vimentin with okadaic acid and withaferin A restored bTubIII- and neurite-associated defects, suggesting its potential to prevent aSyn-mediated neuritic degeneration.
2025-07-16 | PXD063433 | Pride
Project description:Duplication of the SNCA gene (SNCADupl), linked to elevated levels of alpha-synuclein (aSyn), is a genetic cause of Parkinson's disease (PD). Our prior work with human-induced pluripotent stem cell (hiPSC)-derived midbrain neurons generated from PD SNCADupl patients identified neuritic deficits, accompanied by decreased levels of cytoskeletal element b-tubulin-III (bTubIII). To explore the underlying mechanisms for these effects in SNCADupl neurons, we employed CRISPR/Cas9 technology to generate isogenic control hiPSCs. Isogenic correction of SNCA dosage restored SNCADupl-induced neurite morphologic defects and decreased bTubIII levels. Multi-omics analyses revealed SNCADupl-induced upregulation of the cytoskeletal protein vimentin. Further characterization revealed heightened vimentin truncation, associated with altered distribution and organization. Similar changes in vimentin levels and truncation were observed in post-mortem putamen tissue from sporadic PD patients. Notably, interference with vimentin by okadaic acid and withaferin A restored bTubIII- and neurite-associated defects, suggesting that targeting vimentin potentially prevents aSyn-mediated neuritic degeneration.
2025-05-02 | GSE295832 | GEO
Project description:Duplication of the SNCA gene (SNCADupl), linked to elevated levels of alpha-synuclein (aSyn), is a genetic cause of Parkinson's disease (PD). Our prior work with human-induced pluripotent stem cell (hiPSC)-derived midbrain neurons generated from PD SNCADupl patients identified neuritic deficits, accompanied by decreased levels of cytoskeletal element b-tubulin-III (bTubIII). To explore the underlying mechanisms for these effects in SNCADupl neurons, we employed CRISPR/Cas9 technology to generate isogenic control hiPSCs. Isogenic correction of SNCA dosage restored SNCADupl-induced neurite morphologic defects and decreased bTubIII levels. Multi-omics analyses revealed SNCADupl-induced upregulation of the cytoskeletal protein vimentin. Further characterization revealed heightened vimentin truncation, associated with altered distribution and organization. Similar changes in vimentin levels and truncation were observed in post-mortem putamen tissue from sporadic PD patients. Notably, interference with vimentin by okadaic acid and withaferin A restored bTubIII- and neurite-associated defects, suggesting that targeting vimentin potentially prevents aSyn-mediated neuritic degeneration.
2025-05-02 | GSE295831 | GEO
Project description:Vimentin network dysregulation mediates neurite deficits in SNCA duplication 2 Parkinson’s patient-derived midbrain neurons [ATAC-seq]
| PRJNA1256459 | ENA
Project description:To determine sensitivity of a custom 8x60k aCGH design for mosaicism of SNCA gains, a peripheral blood lymphocyte (PBL) DNA sample with a known heterozygous duplication (CN 3, or 50% increase in SNCA) was diluted with a control (wild type, wt) sample (CN 2, screened by MLPA) to create "artifical mosaics" (CN 2.4, 2.3, 2,25, 2.2, 2.15, 2.1). Dilutions, as well as the undiluted heterozygous sample, and the control, were tested, hybridised with Agilent reference DNA.
2016-02-01 | GSE71355 | GEO
Project description:The intermediate filament vimentin is present in immune cells. It provides structural support to cells and functions in macrophages to coordinate inflammatory responses. Neutrophils are an abundance innate immune cell that function by distinct mechanisms from macrophages to mediate antimicrobial activities. The role of vimentin in neutrophils is not established. Here, we developed an immortalized neutrophil model to examine the requirement of vimentin. We demonstrate that vimentin restricts proinflammatory cytokine production and reactive oxygen species production, but enhances phagocytosis and swarming. We observe that vimentin is dispensable for neutrophil extracellular trap (NET) formation, degranulation, and for inflammasome activation. Moreover, gene expression analysis defined vimentin presence was associated with expression changes in multiple genes required for mitochondrial function and ROS overproduction in the absence of vimentin. By treatment of cells producing vimentin with rotenone, an inhibitor for complex I of the electron transport chain, or by treatment of cells lacking vimentin with mitoTEMPO, a SOD mimetic, we complement the changes in ROS levels through manipulation of mitochondrial function. Together, we suggest vimentin regulates neutrophil antimicrobial functions and alters ROS levels through regulation of mitochondrial activity.
2024-09-12 | GSE262717 | GEO
Project description:SNCA, the first gene associated with Parkinson’s disease, encodes the α-synuclein protein, the predominant component within pathological inclusions termed Lewy bodies. We use 3D midbrain organoids, differentiated from human induced pluripotent stem cells derived from patients carrying a triplication of the SNCA gene and from CRISPR/Cas9 corrected isogenic control iPSCs. These human midbrain organoids recapitulate key features of α-synuclein pathology observed in the brains of patients with synucleinopathies. We used single cell RNA sequencing to characterize the cell types within these organoids. We find an equal proportion of neuronal and glial cells. The neuronal populations consist of dopmainergic, excitatory and inhibitory neurons in early and late stages of maturation as well as neural precursor cells. The glial populations consist of dividing radial glia, radial glia, astrocytes and early oligodendorcytes.
2021-11-02 | GSE186780 | GEO
Project description:Purpose:The Vimentin gene plays a pivotal role in epithelial-to-mesenchymal transition (EMT) and is known to be over-expressed in the prognostically poor basal-like breast cancer subtype. Recent studies have reported Vimentin DNA methylation in association with poor clinical outcomes in other solid tumors, but not in breast cancer. We therefore quantified Vimentin DNA methylation in breast tumors and matched normal pairs in association with gene expression and survival in a cohort of 83 breast cancer patients. Materials and Methods:Vimentin methylation was quantified in 14 breast cell lines, 83 breast tumors, and 57 matched normal pairs using MALDI-TOF mass spectrometry. Gene expression data via qRT-PCR in cell lines, and oligo microarray data from breast tissues was correlated with percent methylation in the Vimentin promoter. A threshold of 20 percent average methylation was set for bivariate and multivariate tests of association between methylation and tumor subtype, tumor histopathology, and survival. Results:Vimentin was differentially methylated in luminal breast cancer cell lines, and in luminal A, luminal B and HER2+ breast tumor subtypes, but was rare in basal-like cell lines and tumors. Increased methylation was strongly correlated with decreased mRNA expression in cell lines, and had a moderate inverse correlation in breast tumors. Importantly, Vimentin methylation predicted poor overall survival independent of race, subtype, stage, nodal status or estrogen receptor positivity. Conclusion:Vimentin methylation predicts overall survival in breast cancer patients and holds promise as a prognostic biomarker for guiding treatment and prophylaxis. reference x sample
2013-02-19 | E-GEOD-35629 | biostudies-arrayexpress
Project description:To study the biological and functional role of vimentin in maintenance of the mesenchymal phenotype of mammary epithelial cells, vimentin was silenced in the non-transformed MCF10A cells and vimentin-dependent changes in gene expression were analyzed.
2010-11-18 | GSE17802 | GEO
Project description:To study the biological and functional role of vimentin in maintenance of the mesenchymal phenotype of mammary epithelial cells, vimentin was silenced in the non-transformed MCF10A cells and vimentin-dependent changes in gene expression were analyzed. Scrambled is the siScr-transfected control with two replicates; KD the sample with vimentin knockdown, also two replicates.
2010-11-18 | E-GEOD-17802 | biostudies-arrayexpress