Ten day time course of effect of influenza vaccination on gene expression profiles of spleen cells (unselected cells and B cells) in mice
Ontology highlight
ABSTRACT: Study was to explore the immune and transcriptomic response to seasonal influenza vaccination (TIV) in mice. For more information see Immport study SDY583. 22 total samples, 6 mice per sample: 11 unselected cell samples (0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days post-vaccine boost) and 11 B cell samples (0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days post-vaccine boost)
Project description:Study was to explore the immune and transcriptomic response to seasonal influenza vaccination (TIV) in mice. For more information see Immport study SDY583. 22 total samples, 6 mice per sample: 11 unselected cell samples (0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days post-vaccine boost) and 11 B cell samples (0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days post-vaccine boost)
Project description:Study was to explore the immune and transcriptomic response to seasonal influenza vaccination (TIV) in mice. For more information see Immport study SDY583. 22 total samples, 6 mice per sample: 11 PBMC samples (0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days post-vaccine boost) and 11 B cell samples (0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 days post-vaccine boost)
Project description:We purified FAPs from the hind limbs of wild type, mdx and cardiotoxin-injured mice in order to unveil changes in their transcriptomes. RNA was isolated directly from sorted cells and analyzed by 3’ RNA sequencing.
Project description:Several proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer’s disease (AD), Huntingtin (HTT) for Huntington’s disease, Parkin-2 (PARK-2) for Parkinson’s disease and Ataxin-1 (ATXN-1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD.
Project description:Age-related decline in brain endothelial cell (BEC) function critically contributes to cerebrovascular and neurodegenerative disease. Comprehensive atlases of the BEC transcriptome have become available but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting (MACS)-based mouse BEC enrichment protocol compatible with high-resolution mass-spectrometry and analysed the profiles of protein abundance changes across multiple time points between 3 and 18 months of age and identified Arf6 as one of the most prominently downregulated vesicle-mediated transport protein during BEC aging. To better understand the role of Arf6 in BECs, in this experiment we have compared MACS sorted BECs from Arf6-GFP-AAV vs GFP-AAV treated 3-months-old WT mice and found 86 and 110 proteins to be significantly down- and upregulated, respectively. Enrichment analyses of significantly upregulated proteins revealed vesicle-mediated transport, activation of GTPase activity, and ER to Golgi vesicle-mediated transport to be among the most significantly affected biological processes.
Project description:Age-related decline in brain endothelial cell (BEC) function critically contributes to cerebrovascular and neurodegenerative disease. Comprehensive atlases of the BEC transcriptome have become available but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting (MACS)-based mouse BEC enrichment protocol compatible with high-resolution mass-spectrometry and analysed the profiles of protein abundance changes across multiple time points between 3 and 18 months of age and identified Arf6 as one of the most prominently downregulated vesicle-mediated transport protein during BEC aging. To better understand the role of Arf6 in BECs, in this experiment we have compared MACS sorted BECs from Arf6-KO and WT 3-months-old mice and found 140 and 172 proteins to be significantly down- and upregulated, respectively. Enrichment analyses of significantly downregulated proteins showed mRNA processing to be among the most affected biological processes consistent with our findings on the aged BEC proteome.
Project description:Age-related decline in brain endothelial cell (BEC) function critically contributes to cerebrovascular and neurodegenerative disease. Comprehensive atlases of the BEC transcriptome have become available but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting (MACS)-based mouse BEC enrichment protocol compatible with high-resolution mass-spectrometry based proteomics. In this experiment, first we have compared MACS sorted BECs across multiple time points between 3 and 18 months of age. Using unsupervised cluster analysis, we found a segregation of age-related protein dynamics with biological functions including a downregulation of vesicle-mediated transport. Our approach uncovered changes not picked up by transcriptomic studies such as accumulation of vesicle cargo and receptor ligands including Apoe. Therefor in our next proteomics experiment we compared BECs from 3-months-old Apoe-KO and WT mice and found 111 and 103 proteins to be up- and downregulated, respectively. Comparing the BEC proteomic signature of young Apoe-KO mice with the signature of aged (18-months-old) WT mice we found a positive correlation suggesting an accelerating effect of Apoe deficiency on BEC aging.
Project description:Age-related decline in brain endothelial cell (BEC) function critically contributes to cerebrovascular and neurodegenerative disease. Comprehensive atlases of the BEC transcriptome have become available but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting (MACS)-based mouse BEC enrichment protocol compatible with high-resolution mass-spectrometry based proteomics. In this experiment, we have compared MACS sorted BEC and full brain tissue a massive enrichment of endothelial markers including Nos3, Cdh5, and Pecam1 in BECs compared to FT.
Project description:Cancers are distributed unevenly across the body; but the importance of cell intrinsic factors such as stem cell function in determining organ cancer risk is unknown. Therefore, we used cre-recombination of conditional lineage tracing, oncogene and tumour suppressor alleles to define populations of stem and non-stem cells in mouse organs, and test their life-long susceptibility to tumorigenesis. We show that cancer risk is determined by the life-long generative capacity of mutated cells. This relationship held true in the presence of multiple genotypes and regardless of developmental stage, strongly supporting the notion that stem cells dictate organ cancer risk. Using the liver as a model system, we further show that damage-induced activation of stem cell function markedly increases cancer risk. Therefore, we propose that a combination of stem cell mutagenesis and extrinsic factors that enhance the proliferation of these cell populations, creates a âperfect stormâ that ultimately determines organ cancer risk. Long-term lineage tracing and conditional oncogenic targeting of Prom1-expressing cells in various mouse organs.