Antibodies That Convert Bone Marrow Into Trafficking Microglia-Like Cells Reduce Brain Amyloid
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA418772 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6298160.fastq.gz | Fastqsanger.gz | |||
| SRR6298161.fastq.gz | Fastqsanger.gz | |||
| SRR6298162.fastq.gz | Fastqsanger.gz | |||
| SRR6298163.fastq.gz | Fastqsanger.gz | |||
| SRR6298164.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 9 |
Similar Datasets
Project description:One goal of regenerative medicine is to repair damaged tissue. This requires not only generating new cells of the proper phenotype, but also selecting for those that properly integrate into sites of injury. In our laboratory we are using a cell migration based in vivo selection system to generate antibodies that induce cells to both differentiate and selectively localize to different tissues. Here we describe an antibody that induces bone marrow stem cells to differentiate into microglia-like cells that traffic to the brain where they organize into typical networks. Interestingly, in the APP/PS1 Alzheimer's disease mouse model these induced microglia-like cells are found at sites of plaque formation and significantly reduce their number. These results raise the intriguing question as to whether one can use such antibody-induced differentiation of stem cells to essentially recapitulate embryogenesis in adults to discover cells that can regenerate damaged organ systems.
2017-12-04 | GSE107006 | GEO
Project description:One goal of regenerative medicine is to repair damaged tissue. This requires not only generating new cells of the proper phenotype, but also selecting for those that properly integrate into sites of injury. In our laboratory we are using a cell-migration-based in vivo selection system to generate antibodies that induce cells to both differentiate and selectively localize to different tissues. Here we describe an antibody that induces bone marrow stem cells to differentiate into microglia-like cells that traffic to the brain where they organize into typical networks. Interestingly, in the APP/PS1 Alzheimer's disease mouse model, these induced microglia-like cells are found at sites of plaque formation and significantly reduce their number. These results raise the intriguing question as to whether one can use such antibody-induced differentiation of stem cells to essentially recapitulate embryogenesis in adults to discover cells that can regenerate damaged organ systems.
| S-EPMC5777004 | biostudies-literature
Project description:Serum Amyloid A proteins reduce bone mass during mycobacterial infections
| PRJNA891037 | ENA
Project description:Clusterin (CLU) is one of the most significant genetic risk factors for late onset Alzheimer’s disease. Numerous studies have now demonstrated that CLU-AD mutations and amyloid-β (Aβ) treatment alter the trafficking and localisation of glycosylated CLU. iPSCs with altered CLU trafficking were generated following the removal of CLU exon 2 by CRISPR/Cas9 gene editing. Neurons were generated from control, unedited and exon 2 -/- iPSCs and were incubated with aggregated Aβ peptides. Changes in cell death and neurite length were quantified to determine if altered CLU protein trafficking influenced neuronal sensitivity to Aβ.
2022-07-05 | GSE207466 | GEO
Project description:Genome-wide association studies (GWAS) have identified genes in lipid metabolism,inflammation and vesicular trafficking pathways as risk factors for late onset Alzheimer disease (LOAD). The mechanism by which they cause AD and their relationship to the amyloid cascade affected by genes causing early onset familial AD is unknown. Unproven hypotheses are that these LOAD genes modulate the amyloid cascade itself or downstream targets affected by this cascade.If so, it is likely that these genes and/or other genes in the same pathways may show alterations in their expression as an early consequence of misprocessing of amyloid precursor protein (APP) and accumulation of amyloid β-peptides (Aβ). We report that in three independent APP transgenic mouse models of AD, multiple genes in lipid and inflammation pathways show very early changes in mRNA and protein expression. Many of these changes are reversed by treatment with LXR agonists, which regulate transcription of genes in lipid/inflammation pathways, and which we have previously shown can reverse the cognitive deficits and neuropathology in Tg2756 mice. These results suggest that changes in lipid and inflammation pathways are likely to be very early consequences of APP misprocessing and Aβ accumulation in AD. Moreover, genetic variants within these pathways might affect risk for AD by modulating this early response. These pathways are likely to contain biomarkers of early disease and targets for therapies. TgCRND8 mice and wild-type littermate controls at ages 70, 80, and 150 days (n = 4 mice per cohort) were used in the study.
2014-08-12 | E-GEOD-31372 | biostudies-arrayexpress
Project description:The conversion of cell fates is controlled by hierarchical gene regulatory networks (GRNs) that induce remarkable alterations of cellular and transcriptome states. The identification of key regulators within these networks from myriad of candidate genes, however, poses a major research challenge. Here we present Convert-seq, combining single-cell RNA sequencing (scRNA-seq) and pooled (mutiplexed) ectopic gene expression with a new strategy to discriminate sequencing reads derived from exogenous and endogenous transcripts. We demonstrate Convert-seq by associating hundreds of single cells at multiple time-points during direct conversion of human fibroblasts to induced neurons (iN) with exogenous and endogenous transcriptional signatures. Convert-seq simultaneously identified GRNs that modulate the emergence of parallel developmental trajectories during iN conversion and predicted combinatorial interactions of exogenous transcription factors controlling iN subtype specification. Validation of iN subtypes generated by novel combinations of exogenous transcription factors establish Convert-seq as a broadly applicable workflow to rapidly identify key transcription factors and GRNs orchestrating the direct conversion of virtually any cell type.
2019-12-01 | GSE117075 | GEO
Project description:Decoding neuronal diversity by single cell Convert-seq
| PRJNA481008 | ENA
Project description:Candida albicans is a common commensal on human mucosal surfaces, but can become pathogenic, e.g. if the host is immunocompromised. While neutrophils, macrophages and T cells-driven activation of neutrophils are regarded as major players in the defence against C. albicans, the role of B cells and the protective function of their antibodies are less well characterized. In this study, we show that human serum antibodies are able to enhance the the association of human macrophages with C. albicans cells . Human serum antibodies are also capable of reducing the growth of the fungi as well as inhibiting adhesion to epithelial cells. Furthermore, human serum antibodies impair C. albicans’ invasion into human oral epithelial cells by blocking induced endocytosis and consequently host cell damage. While aspartic proteases secreted by C. albicans were able to cleave human IgG, this process does not appear to affect the protective function of human antibodies in adhesion. Thus, humans are equipped with antiC. albicans antibodies, which can enhance antifungal activities and which can prevent fungal mediated epithelial damage (even in immunocompromised settings).
2022-04-04 | PXD026082 | Pride
Project description:Alzheimer’s Disease (AD) is a disorder characterized by cognitive decline, neurodegeneration, and accumulation of amyloid plaques and tau neurofibrillary tangles in the brain. Dysregulation of epigenetic histone modifications may lead to expression of transcriptional programs that play a role either in protecting against disease genesis or in worsening of disease pathology. One such histone modification, acetylation of histone H3 lysine residue 27 (H3K27ac), is primarily localized to genomic enhancer regions and promotes active gene transcription. We previously discovered H3K27ac to be more abundant in AD patient brain tissue compared to the brains of age-matched non-demented controls. In this study, we use iPSC-neurons derived from familial AD patients with an amyloid precursor protein (APP) duplication (APPDup neurons) as a model to study the functional effect of lowering CBP/P300 enzymes that catalyze H3K27ac. We found that homeostatic amyloid-reducing genes were upregulated in the APPDup neurons compared to non-demented controls. We lowered CBP/P300 to reduce H3K27ac, which led to decreased expression of numerous of these homeostatic amyloid-reducing genes, along with increased extracellular secretion of a toxic amyloid-β species, Aβ(1-42). Our findings suggest that epigenomic histone acetylation, including H3K27ac, drives expression of compensatory genetic programs in response to AD-associated insults, specifically those resulting from APP duplication, and thus may play a role in mitigating AD pathology in neurons.
2023-12-22 | GSE250567 | GEO
Project description:A novel model of amyloid-beta pathology in C. elegans has been generated which allows for substoichiometric fluorescent labeling of amyloid-beta species in living nematodes. By microscopy, FLIM, physiological and biochemical studies, the progress of neurodegeneration and general pathogenicity of amyloidogenic peptides is confirmed. Notably, a single set of neurons was shown to be most vulnerable to Amyloid-beta overexpression and putatively act as a seed for systemic pathogeny. A neuronal version of the amyloid-beta reporter strain was used to perform proteomics analysis from worm lysates after enrichment by immunoprecipitation, using anti-amyloid-beta antibodies.
2020-09-18 | PXD017591 | Pride