Single cell analysis reveals transcriptional changes underlying neurological complications in tuberculous meningitis
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ABSTRACT:
PROVIDER: PRJNA821073 | ENA |
REPOSITORIES: ENA
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Project description:Tuberculous meningitis (TBM) is the most severe and deadly manifestation of tuberculosis. Neurological complications, e.g., hydrocephalus are observed in up to 50% of patients affected. The study of TBM pathogenesis is hampered, at least partially, by a lack of experimental models that recapitulate all clinical features of the human disease. With single-cell transcriptome of blood in tuberculosis revealed, the single cell transcriptome atlas in TBM brain remains yet to be explored. Here, a TBM model was built and then whole brain was dissected for single cell sequencing. Transcriptional changes were observed in all cell types, suggesting a complex biology in TBM pathogenesis. As a result, pervasive immune response was activated by transcription factors Stat1 and IRF1 in macrophages and microglia. For neurons, decreased oxidative phosphorylation activity in neurons links TBM with neurodegenerative diseases. Finally, Ependymal cells show most remarkable transcriptional changes, and decreased Frmd4a may contribute to hydrocephalus and neurodegenerative disorders. We first revealed a comprehensive transcriptome map in TBM mouse model with ScRNA-Seq, and link the cell types, transcriptional genes with regulons and functional processes with neurological complications. These identified cellular and molecular changes offer an unprecedented clue for inspiring the clinical diagnosis and therapeutics of TBM.
2023-08-02 | GSE199649 | GEO
Project description:Tuberculous meningitis is one of the fatal forms of extra pulmonary disease associated with high mortality and severe neurological defects in affected individuals. We have carried out transcriptome level analysis using whole human genome microarrays to identify differential expression of genes between tuberculous meningitis and normals. In our gene expression analysis, we found 2,434 genes that were differentially erexpressed with 2 or more than 2 fold changes between tuberculous meningitis compared to normal cases. Most of the genes encoded many of the proteins, which involves metabolism, energy pathways, cell growth and/or maintenance, transport and cell communication and signal transduction. We have performed immunohistochemistry for the validation of some of the novel candidates identified in our microarray studies.!Series_overall_design = Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups. Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups.!Series_type = Expression profiling by array
2011-06-30 | E-GEOD-23074 | biostudies-arrayexpress
Project description:Tuberculous meningitis is one of the fatal forms of extra pulmonary disease associated with high mortality and severe neurological defects in affected individuals. We have carried out transcriptome level analysis using whole human genome microarrays to identify differential expression of genes between tuberculous meningitis and normals. In our gene expression analysis, we found 2,434 genes that were differentially erexpressed with 2 or more than 2 fold changes between tuberculous meningitis compared to normal cases. Most of the genes encoded many of the proteins, which involves metabolism, energy pathways, cell growth and/or maintenance, transport and cell communication and signal transduction. We have performed immunohistochemistry for the validation of some of the novel candidates identified in our microarray studies.!Series_overall_design = Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups.
2011-07-01 | GSE23074 | GEO
Project description:Tuberculosis co-infected with HIV may increase the risk of causing meningitis. Tuberculous meningitis co-infected with HIV associated with high mortality and severe neurological abnormalities in affected individuals. We have carried out TBM co-infected with HIV gene expression study using whole human genome microarrays. We identified 796 differentially expressed genes with fold change cut off of 2 or more than 2. Out of 796 differentially expressed genes, 398 were upregulated and 396 were downregulated. We have validated two molecules from microarray data using immunohistochemistry. The proposed study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis coinfected with HIV and four head injury cases were used as controls. We have used 4X44K arrays from agilent platform. To validate our microarray results, we have done immunohistochemistry on 10 TBM+HIV cases and 10 control groups.
2012-12-31 | E-GEOD-29507 | biostudies-arrayexpress
Project description:Whole blood transcriptional profiles in children with or without tuberculous meningitis (TBM) were compared using RNA-Seq and a biomarker signature driven by inflammasome activation and signaling was identified
2019-08-06 | GSE111459 | GEO
Project description:Tuberculosis co-infected with HIV may increase the risk of causing meningitis. Tuberculous meningitis co-infected with HIV associated with high mortality and severe neurological abnormalities in affected individuals. We have carried out TBM co-infected with HIV gene expression study using whole human genome microarrays. We identified 796 differentially expressed genes with fold change cut off of 2 or more than 2. Out of 796 differentially expressed genes, 398 were upregulated and 396 were downregulated. We have validated two molecules from microarray data using immunohistochemistry.
2012-12-31 | GSE29507 | GEO
Project description:Cerebrospinal fluid transcriptional profiles in children with tuberculous meningitis (TBM) or other infections were compared using RNA-Seq and a biomarker signature driven by NMDA-receptor activation was identified
2019-08-06 | GSE122377 | GEO
Project description:Tuberculous Meningitis in Pediatric Patients
| PRJNA437114 | ENA
Project description:Tuberculous Meningitis in Pediatric Patients [CSF]
| PRJNA504827 | ENA
Project description:In order to identify the potential biomarkers for discriminating tuberculous meningitis (TBM) and viral meningitis (VM) and to reveal the different pathophysiological processes between TBM and VM, a genome-wide miRNA screenings of peripheral blood mononuclear cells (PBMCs) from TBM, VM, and healthy controls (HCs) using microarray assay was performed (12 samples). Twenty-eight differentially expressed miRNAs were identified between TBM and VM, and 11 differentially expressed miRNAs were identified between TBM and HCs. The 6 overlapping miRNAs detected in both TBM vs. VM and TBM vs. HCs were verified by qPCR analysis and showed a 100% consistent result with that in microarray test.
2019-10-02 | GSE131708 | GEO