Control (healthy) iPSC-derived astrocytes treated with: Media (control) or aSYN F110 10uM
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PROVIDER: PRJNA701929 | ENA |
REPOSITORIES: ENA
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Project description:Control (healthy) iPSC-derived astrocytes treated with: Media (control), TNFa 100ug/ml, Monomeric aSYN 10uM, or Fibril aSYN 10uM
| PRJNA701928 | ENA
Project description:The overall goal was to identify changes in gene expression following treatment with aSYN F110 compared to control (untreated). Alpha-synuclein (αSYN) protein has been observed in reactive astrocytes in PD patients’ brains, raising the question of how αSYN, neuroinflammation, and astrocytes interact in PD pathogenesis. Here, we examined the cellular changes triggered by tumor necrosis factor alpha (TNFα) and different αSYN species in astrocytes derived from induced pluripotent stem cells. Human astrocytes treated with TNFα displayed a strong reactive pro-inflammatory phenotype with upregulation of pro-inflammatory gene networks, activation of the NF-kB pathway, and release of pro-inflammatory cytokines, whereas those treated with high molecular weight αSYN fibrils acquired a reactive antigen (cross-)presenting phenotype with upregulation of MHC genes and increased HLA-DR/DQ/DP and HLA-F molecules at the cell surface. Surprisingly, cell surface location of MHC proteins was abrogated by larger F110 fibrils polymorph, despite the upregulation of MHC genes. A proteomics investigation further confirmed a direct interaction between astrocytic MHC proteins and αSYN fibril peptides. Interestingly, TNFα and αSYN fibrils competed to drive the astrocyte immune reactive response. The astrocyte immune responses were accompanied by an impaired ATP-generating mitochondrial respiration, which was exacerbated in PD astrocytes containing a PARK2-variant. Our data provide evidence for astrocytic involvement in PD pathogenesis and reveal their complex immune reactive responses to exogenous stressors.
2021-02-16 | GSE166769 | GEO
Project description:The overall goal was to identify changes in gene expression following treatment with TNFa, monomeric, or fibril aSYN compared to control (untreated). Alpha-synuclein (αSYN) protein has been observed in reactive astrocytes in PD patients’ brains, raising the question of how αSYN, neuroinflammation, and astrocytes interact in PD pathogenesis. Here, we examined the cellular changes triggered by tumor necrosis factor alpha (TNFα) and different αSYN species in astrocytes derived from induced pluripotent stem cells. Human astrocytes treated with TNFα displayed a strong reactive pro-inflammatory phenotype with upregulation of pro-inflammatory gene networks, activation of the NF-kB pathway, and release of pro-inflammatory cytokines, whereas those treated with high molecular weight αSYN fibrils acquired a reactive antigen (cross-)presenting phenotype with upregulation of MHC genes and increased HLA-DR/DQ/DP and HLA-F molecules at the cell surface. Surprisingly, cell surface location of MHC proteins was abrogated by larger F110 fibrils polymorph, despite the upregulation of MHC genes. A proteomics investigation further confirmed a direct interaction between astrocytic MHC proteins and αSYN fibril peptides. Interestingly, TNFα and αSYN fibrils competed to drive the astrocyte immune reactive response. The astrocyte immune responses were accompanied by an impaired ATP-generating mitochondrial respiration, which was exacerbated in PD astrocytes containing a PARK2-variant. Our data provide evidence for astrocytic involvement in PD pathogenesis and reveal their complex immune reactive responses to exogenous stressors.
2021-02-16 | GSE166768 | GEO
Project description:The goal of this study is to compare the mRNA transcriptome of astrocytes treated with Activated Microglia and Endothelial conditioned media
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Project description:Huntington's disease (HD) and control GLAST-postive induced pluripotent stem cell (iPSC)-derived astrocytes underwent single-nucleus RNA-sequencing to investigate cell state diversity across control and HD patient-derived astrocytes.
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Project description:Astrocytes are instrumental in both maintaining CNS homeostasis and responding to tissue injury. While astrocyte activation may be a beneficial response to acute pathologies, prolonged reactive gliosis is thought to be injurious in neurodegenerative diseases, including multiple sclerosis (MS). A major limitation of studying neurodegenerative diseases is lack of human pathological specimens obtained during the acute stages, thereby relegating research to post mortem specimens often obtained years after the initiation of pathology. Rodent reactive astrocytes have been shown to be cytotoxic to neurons and oligodendrocytes but may differ from human cells, especially in diseases with known genetic susceptibility. Herein, we purified human CD49f+ astrocytes from differentiated induced pluripotent stem cells derived from individual patient and control peripheral white blood cell samples. We compared TNF and IL1a stimulated human reactive astrocytes from 7 persons with MS and 6 non-MS controls and show their specific astrocyte transcriptomic profiles are remarkably similar to those described in rodents. The functional effect of astrocyte conditioned media (ACM) was examined in a human oligodendrocyte precursor cell (OPC) line differentiation assay using a transgenic secreted reporter of myelin basic protein (MBP) expression. ACM was not cytotoxic to the OPCs but robustly inhibited the MBP reporter. No differences were seen between MS and control stimulated astrocytes at either the transcript level or in functional OPC suppression assays. We next used RNAseq to interrogate differentially expressed genes in the OPC lines that had suppressed differentiation from the human ACM. Remarkably, not only was OPC differentiation and myelin gene expression suppressed, but we observed induction of several immune pathways and Nf-κB signaling in OPCs exposed to the ACM. These data support the notion that reactive astrocytes can inhibit OPC differentiation thereby limiting their remyelination capacity, and that OPCs take on an immune profile in the context of inflammatory cues.
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Project description:Transcriptional profiling of mouse primary astrocytes comparing control untreated astrocytes with astrocytes treated with recombinant LCN2 protein (10 micro gram/ml). Goal was to determine the effects of LCN2 treatment on global gene expression in astrocytes. A secreted protein lipocalin-2 (LCN2) has been implicated in diverse cellular processes including cell morphology and migration. We have previously demonstrated that lcn2 mediates reactive astrocytosis. In order to further understand the role of lcn2 in the CNS, astrocyte transcriptome was analyzed following LCN2 treatment. Chemokines were the major group of genes upregulated by LCN2. Two-condition experiment, control untreated astrocytes vs. LCN2 protein treated astrocytes. Biological replicates: 1 control replicates, 1 treated replicates.
2012-06-29 | E-GEOD-15667 | biostudies-arrayexpress
Project description:RNA-Sequencing of Astrocytes Stimulated with Activated Endothelial conditioned media (ECM) and Activated Microglia conditioned media (MCM)
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Project description:Schizophrenia is a complex and severe neuropsychiatric disorder, with a wide range of debilitating symptoms. Several aspects of its multifactorial complexity are still unknown, and some are accepted to be an early developmental deficiency with a more specifically neurodevelopmental origin. ??Molecular and functional abnormalities in astrocytes play a role in the etiology and pathogenesis of schizophrenia. In this study, human induced pluripotent stem cells (hiPSC)-derived astrocytes from schizophrenia patients were investigated regarding their proteome, inflammatory responses, and their secretome effect on vascularization. Proteomic analysis revealed alterations in proteins related to immune function and vascularization. Taken together, our results suggest that schizophrenia astrocytes are immunologically dysfunctional which might affect vascularization through secreted factors.
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Project description:Transcriptional profiling of Neisseria meningitidis strain MC58 grown on RPMI agar containing 10uM Transferrin, 10uM Lactoferrin, 1uM Haemoglobin, or 20uM Ferric chloride.
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