TRAP-seq of mouse astrocytes involved in central nervous system remyelination
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ABSTRACT:
PROVIDER: PRJEB39118 | ENA |
REPOSITORIES: ENA
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Project description:Remyelination failure contributes to axonal dysfunction in neurodegenerative disorders. But whether astrocytes, the most abundant glial cell type in demyelinated lesions, support or impede remyelination is controversial. Following focal demyelinated lesions of the mouse corpus callosum induced with the myelin toxin lysolecithin, we used TRAP (translational ribosome affinity purification) sequencing to isolate and sequence ribosome-associated mRNAs which are being actively translated in astrocytes, and studied how the responses and molecular mechanisms in astrocytes are linked to remyelination.
2023-05-17 | E-MTAB-9270 | biostudies-arrayexpress
Project description:Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells – astrocytes and mature myelin-forming oligodendrocytes – is a critical determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation. Remyelination fails following sustained astrocytic Nrf2 activation in focally-lesioned mice yet is restored by either cholesterol biosynthesis/efflux stimulation, or Nrf2 inhibition using the existing therapeutic Luteolin. We identify that astrocyte-oligodendrocyte interaction regulates remyelination, and reveal a drug strategy for central nervous system regeneration centred on targeting this interaction.
2023-05-17 | PXD041850 | Pride
Project description:Failure of remyelination in multiple sclerosis (MS) is associated with inhibition of oligodendrocyte precursor (OPC) differentiation, but the cellular and molecular mechanisms involved remain poorly understood. We now report inflammatory demyelination in MS is associated with localized expression of fibroblast growth factor 9 (FGF9) by oligodendrocytes and to a lesser extent astrocytes, and demonstrate FGF9 inhibits myelination and remyelination in vitro. This inhibitory activity is reversible and due to an off target FGF9-dependent effect on astrocytes that disrupts in the growth factor milieu required to support myelination. We identify multiple downstream events induced by FGF9 associated with this effect including increased expression of leukaemia inhibitory growth factor (LIF) and FGF2, both of which are shown to inhibit myelination if present in excess. These studies identify FGF9-dependent signal transduction in astrocytes as a novel target for therapeutic strategies designed to enhance remyelination by endogenous OPC in MS. Gene expression profiles of rat myelinating cultures grown in the presence or absence of FGF9 (100 ng/ml) for 24h and 10 days were generated using Affymetrix GeneChip® Rat Gene 1.0 ST Arrays. Each time point (T1: 24 hrs, and T2: 10 days) has Control (CTR) and Treatment (FGF) groups, with two replicates in each group. In total, 8 arrays were generated from the four groups (CTR-T1, CTR-T2, FGF-T1 and FGF-T2).
2016-02-17 | E-GEOD-44562 | biostudies-arrayexpress
Project description:Failure of remyelination in multiple sclerosis (MS) is associated with inhibition of oligodendrocyte precursor (OPC) differentiation, but the cellular and molecular mechanisms involved remain poorly understood. We now report inflammatory demyelination in MS is associated with localized expression of fibroblast growth factor 9 (FGF9) by oligodendrocytes and to a lesser extent astrocytes, and demonstrate FGF9 inhibits myelination and remyelination in vitro. This inhibitory activity is reversible and due to an off target FGF9-dependent effect on astrocytes that disrupts in the growth factor milieu required to support myelination. We identify multiple downstream events induced by FGF9 associated with this effect including increased expression of leukaemia inhibitory growth factor (LIF) and FGF2, both of which are shown to inhibit myelination if present in excess. These studies identify FGF9-dependent signal transduction in astrocytes as a novel target for therapeutic strategies designed to enhance remyelination by endogenous OPC in MS.
2016-02-17 | GSE44562 | GEO
Project description:Alzheimer’s disease is known to alter astrocytes, but the effect of Aß and Tau pathology on these cells remains poorly understood. We investigated the transcriptomic behaviour of astrocytes (via translating ribosome affinity purification (TRAP)), and bulk brain tissue, in mouse models of APP/PS1 ß-amyloidopathy and MAPT-P301S tauopathy, in a mouse model overexpressing cytoprotective Nrf2 specifically in astrocytes (GFAP-Nrf2 model), and in crosses between the amyloidopathy and tauopathy models with the GFAP-Nrf2 mouse.
2021-12-02 | E-MTAB-10985 | biostudies-arrayexpress
Project description:3' mRNA-sequencing of the immunoprecipitated and supernatant fractions after Translating Ribosome Affinity Purification (TRAP) targeted to hypothalamic astrocytes RNA (from Aldh1l1eGFP-L10a mice) for 3 experimental conditions: chow diet; high-fat diet; high-fat diet + orchiectomy (Sham-chow n=7, Sham-HFD n=6, ORX-HFD n=7)
2023-04-03 | GSE214683 | GEO
Project description:TRAP translational profiling is a method that allows investigators to genetically characterize specific cell types in complex tissues such as mouse brain. Using this technique we obtained RNA-Seq data from actively translating transcripts present in ependymal cells lining the ventricles in the central nervous system of adult Dcdc2a-EGFP/Rpl10a (ES2575) mice
2019-11-20 | GSE140680 | GEO
Project description:Hypothalamic astrocytes TRAP-seq in ORX/HFD mice
| PRJNA886669 | ENA
Project description:The local production of IFN-γ is important to control Toxoplasma gondii in the brain but the basis for these protective effects are not fully understood. The studies presented here reveal that the ability of IFN-γ to inhibit parasite replication in astrocytes in vitro is dependent on signal transducer and activator of transcription 1 (STAT1) and that mice that specifically lack STAT1 in astrocytes are unable to limit parasite replication in the central nervous system (CNS). This susceptibility is associated with a loss of anti-microbial pathways but also altered local immune responses that include decreased T cell production of IFN-γ and elevated expression of inhibitory receptors. These results identify a critical role for astrocytes in limiting the replication of an important opportunistic pathogen and highlight their role in coordinating local anti-parasitic responses.
2016-10-20 | GSE67137 | GEO
Project description:Remyelinating substances could be an essential supplement to immunomodulatory medications, optimizing the treatment of multiple sclerosis (MS) patients. Fingolimod is a sphingosine-1-phosphate receptor (S1PR) modulator and crosses the blood-brain barrier. Central nervous system (CNS) cells express S1PRs, and Fingolimod could theoretically improve CNS remyelination and be neuroprotective per se, but data are inconsistent. We used the cuprizone model for investigating the effect of fingolimod on remyelination and axonal damage by Immunohistochemistry and quantitative mass spectrometry. After three weeks of remyelination, fingolimod-treated mice had more mature oligodendrocytes in the secondary motor cortex than the placebo group. However, fingolimod did not at any time point affect remyelination or axonal damage. We conclude that fingolimod does not promote remyelination or protect against axonal injury or loss after cuprizone exposure.
2019-11-20 | PXD012676 | Pride