Integrative analysis of altered genes expressed in human Alzheimer’s disease brain
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PROVIDER: PRJNA727603 | ENA |
REPOSITORIES: ENA
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Project description:Integrative analysis of altered genes expressed in human Alzheimer’s disease brain (RNA-Seq)
| PRJNA727602 | ENA
Project description:We had previously performed comparative gene expression profiling of human postmortem Alzheimer’s disease (AD) brains donated for the Hisayama study. The hippocampi from AD brains showed the most significant alteration in gene expression profile [PMID: 23595620]. In the present study, in order to identify molecular pathological alterations in AD hippocampus, we applied human transcriptome array and RNA-sequencing to the same samples and reanalyzed the gene array data, and performed integrative analysis of all 3 methods. We also applied gene array to hippocampus of 6-month-old AppNL-G-F/NL-G-F knock-in AD model mice as a preclinical AD stage model, and at last we performed the interspecies comparison. Functional annotation clustering with the results of all 3 or at least 2 methods in human, showed synapse, cell junction, calmodulin binding, ion transport and glycoproteins as the top affected terms. In hippocampi of AppNL-G-F/NL-G-F mice which exhibit significant amyloidosis but not neuronal degeneration, we found that expression of genes categorized in signaling specially signaling peptides with disulfide bond or glycoproteins, together with the innate immune response and lysosome of cells are upregulated. Comparing the extended human data with mouse data, we found and confirmed by qRT-PCR, 2 common up-regulated genes, Clec7a and C4b, which induce innate immune response and synapse elimination. We also found and confirmed by qRT-PCR, 2 common down-regulated genes, one is Slc17a6, which can affect synaptic transmission of glutamate, and second one is Rxfp1, which is involved in gene transcription. Amyloid-beta accumulation is the major hallmark of AD at 6 month-old AppNL-G-F/NL-G-F mice, therefore our data suggests that amyloid-beta accumulation induces innate immune response, synapse elimination, besides it can decreases glutamate transmission, and affect gene transcription in early stage of hippocampal AD brain, prior to neuronal degeneration.
2024-12-31 | GSE173954 | GEO
Project description:We had previously performed comparative gene expression profiling of human postmortem Alzheimer’s disease (AD) brains donated for the Hisayama study. The hippocampi from AD brains showed the most significant alteration in gene expression profile [PMID: 23595620]. In the present study, in order to identify molecular pathological alterations in AD hippocampus, we applied human transcriptome array and RNA-sequencing to the same samples and reanalyzed the gene array data, and performed integrative analysis of all 3 methods. We also applied gene array to hippocampus of 6-month-old AppNL-G-F/NL-G-F knock-in AD model mice as a preclinical AD stage model, and at last we performed the interspecies comparison. Functional annotation clustering with the results of all 3 or at least 2 methods in human, showed synapse, cell junction, calmodulin binding, ion transport and glycoproteins as the top affected terms. In hippocampi of AppNL-G-F/NL-G-F mice which exhibit significant amyloidosis but not neuronal degeneration, we found that expression of genes categorized in signaling specially signaling peptides with disulfide bond or glycoproteins, together with the innate immune response and lysosome of cells are upregulated. Comparing the extended human data with mouse data, we found and confirmed by qRT-PCR, 2 common up-regulated genes, Clec7a and C4b, which induce innate immune response and synapse elimination. We also found and confirmed by qRT-PCR, 2 common down-regulated genes, one is Slc17a6, which can affect synaptic transmission of glutamate, and second one is Rxfp1, which is involved in gene transcription. Amyloid- accumulation is the major hallmark of AD at 6 month-old AppNL-G-F/NL-G-F mice, therefore our data suggests that amyloid- accumulation induces innate immune response, synapse elimination, besides it can decreases glutamate transmission, and affect gene transcription in early stage of hippocampal AD brain, prior to neuronal degeneration.
2021-12-23 | GSE173955 | GEO
Project description:The blood-brain barrier (BBB) is primarily manifested by a variety of physiological properties of brain endothelial cells (ECs), but the molecular foundation for these properties remains incompletely clear. Here, we generate a comprehensive molecular atlas of adult brain ECs using acutely purified mouse ECs and integrated multi-omics. Using RNA-seq and proteomics, we identify the transcripts and proteins selectively enriched in brain ECs and demonstrate that they are partially correlated. Using single-cell RNA-seq, we dissect the molecular basis of functional heterogeneity of brain ECs. Using integrative epigenomics and transcriptomics, we determine that TCF/LEF, SOX, and ETS families are top-ranked transcription factors regulating the BBB. We then validate the identified brain EC-enriched proteins and transcription factors in normal mouse and human brain tissue, and assess their expression changes in mice with Alzheimer’s disease. Overall, we present a valuable resource with broad implications for the BBB regulation and treatment of neurological disorders.
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Project description:Integrative multi-omic profiling of adult mouse brain endothelial cells and potential implications in Alzheimer’s disease
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Project description:We performed a large-scale, site-specific N-glycoproteome profiling study of human Alzheimer’s disease (AD) and control brains using mass spectrometry–based quantitative N-glycoproteomics. The study provided a system-level view of human brain N-glycoproteins and in vivo N-glycosylation sites and identified disease signatures of altered N-glycopeptides, N-glycoproteins, and N-glycosylation site occupancy in AD. Glycoproteomic data-driven network analysis showed 13 modules of co-regulated N-glycopeptides/glycoproteins, 6 of which are associated with AD phenotypes.
2022-11-02 | PXD037229 | Pride
Project description:To investigate the presence of piRNAs and their potential functions in human brain and neurodegenerations, we performed the genomic profiling in Healthy Brain (HB) sample as well as Alzheimer-affected brain (AD) sample by adopting Next-Gen small RNA sequencing technology. Using deep sequencing of small RNAs, we identified an extensive catalogue of 564 and 451 mature piRNAs in HB and AD respectively. The piRNAs from each sample exhibited varied length distribution between 26-32 nts and are originated from different genomic locations. We found 149 piRNAs to be differentially expressed in Alzheimer’s disease which comprises of 146 up-regulated and 3 down-regulated piRNAs. Ours is the first study that reported the presence of piRNAs in healthy as well as Alzheimer’s disease-affected human brain. The extensive catalogue of human piRNAs detected in this study provides a useful resource for decrypting the involvement of piRNAs in neurological functions as well as neurodegenerations.
2017-01-28 | GSE85075 | GEO
Project description:Blood-brain barrier (BBB) critically regulate the homeostasis of central nervous system (CNS). This barrier property allows cerebral vessels to meet the extremely high metabolic demand of neural activities and meanwhile protect sensitive neurons from toxic plasma components, blood immune cells and xenobiotics. Therefore, a comprehensive inventory of the molecular determinants of BBB would substantially facilitate understanding of the pathogenesis of neurological disorders involving BBB dysfunction and promote development of novel CNS drug delivery strategies. Here, we established the proteome activity landscapes of adult mouse brain, lung and liver ECs. In this study, we produced a comprehensive molecular atlas of adult mouse BBB and revealed novel insights into adult BBB in health and Alzheimer’s disease.
2023-11-01 | PXD029195 | Pride
Project description:Proteogenomics is an emerging approach to improve gene annotation and interpretation of proteomics data. Here we present JUMPg, an integrative proteogenomics pipeline including customized database construction, tag-based database search, peptide-spectrum match filtering, and data visualization. JUMPg creates multiple databases of DNA polymorphisms, mutations, splice junctions, partially trypticity, as well as protein fragments translated from the whole transcriptome in all six frames after RNA-seq de novo assembly. We use a multistage strategy to search these databases sequentially, in which the performance is optimized by re-searching only unmatched high quality spectra, and re-using amino acid tags generated by the JUMP search engine. The identified peptides/proteins are displayed with gene loci using the UCSC genome browser. The JUMPg is applied to process a label-free mass spectrometry dataset of Alzheimer’s disease postmortem brain, uncovering 496 new peptides of amino acid substitutions, alternative splicing, frame shift, and “non-coding gene” translation. The novel protein PNMA6BL specifically expressed in the brain is highlighted. We also tested JUMPg to analyze a stable-isotope labeled dataset of multiple myeloma cells, revealing 991 sample-specific peptides that include protein sequences in the immunoglobulin light chain variable region. Thus, the JUMPg program is an effective proteogenomics tool for multi-omics data integration.
2017-02-20 | PXD004010 | Pride
Project description:Profiling of post-mortem brain microRNA in Alzheimer’s disease
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