Circadian clock-mediated neuronal gene expression in Aβ toxicity and excitotoxicity
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ABSTRACT:
PROVIDER: PRJNA849149 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR19648043.fastq.gz | Fastqsanger.gz | |||
| SRR19648045.fastq.gz | Fastqsanger.gz | |||
| SRR19648046.fastq.gz | Fastqsanger.gz | |||
| SRR19648048.fastq.gz | Fastqsanger.gz |
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Project description:In recent decades, transcriptome analysis has been widely used to understand human disease pathogenesis and identify therapeutic targets and biomarkers. Accumulated reports in patients with neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, have also provided evidence of dysregulated gene expression related to neuropathogenesis. However, obtaining samples from neurodegenerative patients is more challenging than other human diseases due to low accessibility. Also, brain tissues and cerebrospinal fluid are composed of multiple cell types, so they are unsuitable for obtaining neural cell-type-specific gene expression profiles. Thus, we here report gene expression profiles in primary neuronal cultures exposed to Aβ toxicity and glutamate excitotoxicity to understand pathological gene expression in neurons. By RNA-sequencing analysis, we compare transcriptomes and find that two groups of genes show similar expression patterns in Aβ toxicity excitotoxicity—they are either up- or down-regulated in both conditions. Genes in the two groups are related to synaptic function and cell signaling, which are well-known biological functions altered in Aβ toxicity and excitotoxicity. Interestingly, the analysis reveals a possibility that circadian clock (molecular oscillator generating daily rhythms)-related genes are dysregulated in both conditions. We confirm the reduced circadian transcription factor Bmal1 levels in Aβ toxicity and glutamate excitotoxicity. RNA-sequencing analysis in Bmal1-deleted neurons shows potential relationships between BMAL1 and synaptic functions. Thus, this transcriptome study provides evidence of the potential roles of the circadian clock in neuropathogenesis.
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We provide for the first time a potential molecular link between severity of Type 2 diabetes and circadian clock machinery, which paves a way for further mechanistic understanding of circadian oscillator changes upon Type 2 diabetes in humans.
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Project description:The circadian clock is comprised of proteins that form negative feedback loops, which regulate the timing of global gene expression in a coordinated 24 hour cycle. As a result, the plant circadian clock is responsible for regulating numerous physiological processes central to growth and survival. To date, most plant circadian clock studies have relied on diurnal transcriptome changes to elucidate molecular connections between the circadian clock and observable phenotypes in wild-type plants. Here, we have combined high-throughput RNA-sequencing and mass spectrometry to comparatively characterize the lhycca1, prr7prr9, gi and toc1 circadian clock mutant rosette transcriptome and proteome at the end-of-day and end-of-night.
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Project description:Circadian rhythms are a series of endogenous autonomous 24-hour oscillations generated by the circadian clock. At the molecular level, the circadian clock is generated by a transcription-translation feedback loop, where BMAL1 and CLOCK transcription factors of the positive arm activate the expression of CRYPTOCHROME and PERIOD (PER) genes of the negative arm as well as the circadian clock-regulated genes. In this project, we aimed at finding the interactome of PER2 protein in human U2OS osteosarcoma cell line using proximity-dependent biotin identification (BioID) technique. U2OS clones overexpressing PER2-BioID2 or BioID2 were treated with dexamethasone in order to reset the circadian rhythm, and cells were then incubated in biotin-containing media for 12 hours to label the proteins in close proximity of PER2-BioID2. Samples were collected after 36 and 48 hours of the resetting to identify the labeled proteins by mass spectrometry. In addition to known interactors such as CRY1 and CRY2, many novel interactors were identified. In summary, we obtained a network of PER2 interactome and confirmed some of the novel interactions using classical the co-immunoprecipitation method.
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Analysis of differential protein expression in the hemolymph from flies reared on a high protein diet. Comparison of flies with and without a functional circadian clock within their photoreceptors.
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