RNA-sequencing analysis of pro-inflammatory cytokine stimulation of HMC3 microglia and HOG oligodendroglioma cell lines
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA824292 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18671840.fastq.gz | Fastqsanger.gz | |||
| SRR18671841.fastq.gz | Fastqsanger.gz | |||
| SRR18671842.fastq.gz | Fastqsanger.gz | |||
| SRR18671843.fastq.gz | Fastqsanger.gz |
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Project description:The study aims to utilize RNA-seq to characterize the transcriptomic alterations in TIA1-knockdown HMC3 cells compared to control cells, with the goal of identifying differentially expressed genes and elucidating the molecular pathways and biological processes regulated by TIA1, a key RNA-binding protein. By profiling gene expression changes following TIA1 depletion, the research seeks to uncover how this protein influences cellular functions in HMC3 cells, a model of human microglia critical for central nervous system immunity and homeostasis. Given the established role of TIA1 in mRNA metabolism and its links to neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), this study holds relevance for understanding microglial gene regulatory mechanisms disrupted in disease contexts. Identifying TIA1-dependent transcriptomic signatures in HMC3 cells can provide insights into the functional consequences of TIA1 dysfunction in microglia, potentially revealing novel therapeutic targets or biomarkers for neurological diseases while advancing our understanding of RNA-mediated regulatory networks in immune cells of the brain.
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Project description:The ability to sense and adapt to a hostile host environment is a crucial element for virulence of pathogenic fungi, including Cryptococcus neoformans. These cellular responses are evoked by diverse signaling cascades, including the stress-activated HOG pathway. Despite previous analysis of central components of the HOG pathway, its downstream signaling network is poorly characterized in C. neoformans. Here we performed comparative transcriptome analysis with HOG signaling mutants to explore stress-regulated genes and their correlation with the HOG pathway in C. neoformans. In this study we not only provide important insights into remodeling patterns of global gene expression for counteracting external stresses, but also elucidated novel characteristics of the HOG pathway in C. neoformans. First, inhibition of the HOG pathway increases expression of ergosterol biosynthesis genes and cellular ergosterol content, conferring a striking synergistic antifungal activity with amphotericin B and providing an excellent opportunity to develop a novel therapeutic method for treatment of cryptococcosis. Second, a number of cadmium-sensitive genes are differentially regulated by the HOG pathway, and their mutation causes resistance to cadmium. Finally, we have discovered novel stress-defense and HOG-dependent genes, which encodes a sodium/potassium efflux pump, protein kinase, multidrug transporter system, and elements of the ubiquitin-dependent system.
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Project description:The ability to sense and adapt to a hostile host environment is a crucial element for virulence of pathogenic fungi, including Cryptococcus neoformans. These cellular responses are evoked by diverse signaling cascades, including the stress-activated HOG pathway. Despite previous analysis of central components of the HOG pathway, its downstream signaling network is poorly characterized in C. neoformans. Here we performed comparative transcriptome analysis with HOG signaling mutants to explore stress-regulated genes and their correlation with the HOG pathway in C. neoformans. In this study we not only provide important insights into remodeling patterns of global gene expression for counteracting external stresses, but also elucidated novel characteristics of the HOG pathway in C. neoformans. First, inhibition of the HOG pathway increases expression of ergosterol biosynthesis genes and cellular ergosterol content, conferring a striking synergistic antifungal activity with amphotericin B and providing an excellent opportunity to develop a novel therapeutic method for treatment of cryptococcosis. Second, a number of cadmium-sensitive genes are differentially regulated by the HOG pathway, and their mutation causes resistance to cadmium. Finally, we have discovered novel stress-defense and HOG-dependent genes, which encodes a sodium/potassium efflux pump, protein kinase, multidrug transporter system, and elements of the ubiquitin-dependent system. There is more than 95% genome homology between JEC21 (Cryptococcus neoformans var. neoformans serotype D) and H99 (Cryptococcus neoformans var. grubii serotype A). Therefore, 100 slides of JEC21 70-mer oligo arrays are used in this analysis. 3 biological replicate experiments are performed. Total RNAs are extracted under 3 conditions (1M NaCl, 20ug/ul Fludioxonil, 2.5mM Hydrogen peroxide) at 3 time points (0time, 30min, 60min) with 4 strains from H99 (wild type, hog1Î , ssk1Î , skn7Î). We use a mix of all the total RNAs from this experiment as the control RNA. We use Cy5 as the sample dye and Cy3 as the control dye. Several samples are dye swapped.
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