The mammalian brain is complex, with multiple cell types performing a variety of diverse functions, but exactly how each cell type is affected in aging remains largely unknown. Here we performed a single-cell transcriptomic analysis of young and old mouse brains. We provide comprehensive datasets of aging-related genes, pathways and ligand–receptor interactions in nearly all brain cell types. Our analysis identified gene signatures that vary in a coordinated manner across cell types and gene sets that are regulated in a cell-type specific manner, even at times in opposite directions. These data reveal that aging, rather than inducing a universal program, drives a distinct transcriptional course in each cell population, and they highlight key molecular processes, including ribosome biogenesis, underlying brain aging. Overall, these large-scale datasets provide a resource for the neuroscience community that will facilitate additional discoveries directed towards understanding and modifying the aging process. Overall design: Total of 16 mice brains with raw data for 50,212 single cells and processed data for 37,089 single cells
Single-cell transcriptomic profiling of the aging mouse brain.
Specimen part, Subject
View SamplesRNA-seq was performed using the RNA extracted from the bottom half of right lobe of mouse livers. Mice fall into two groups, mutant group which express ectopic hURI and their control littermates which do not express hURI. Two time points were considered in the study, 1-week-old mice, expressing hURI since 1 week (n =3, 4 for control and mutant, respectively) and 8-week-old mice expressing hURI since 8 week (n= 4, 3 for control and mutant, respectively), as hURI is expressed since conception. Overall design: Determination of differentially expressed transcripts over two time points (1 week and 8 weeks) in mouse livers expressing hURI (1 week and 8 weeks).
Inhibition of de novo NAD(+) synthesis by oncogenic URI causes liver tumorigenesis through DNA damage.
Specimen part, Subject
View SamplesSenescence is a cellular phenotype present in health and disease, characterized by a stable cell cycle arrest and an inflammatory response, denominated senescence-associated secretory phenotype (SASP). The SASP is important in influencing the behaviour of neighbouring cells and altering the microenvironment; yet, this role has been mainly attributed to soluble factors. Here, we show that both the soluble factors in addition to small extracellular vesicles (sEV) are capable of transmitting paracrine senescence to nearby cells. Analysis of individual cells internalizing sEV, using a Cre-reporter system, show a positive correlation between sEV uptake and senescence activation. Interestingly, we find an increase in the number of multivesicular bodies during senescence in vivo. sEV protein characterization by mass spectrometry (MS) followed by a functional siRNA screen identify the Interferon Induced Transmembrane Protein 3 (IFITM3) as partially responsible for transmitting senescence to normal cells. Altogether, we found that sEV contribute to paracrine senescence. Overall design: SASP related mRNA transcripts in HFFF2 treated with sEV from iRAS cells in comparison with HFFF2 treated with sEV from iC cells
Small Extracellular Vesicles Are Key Regulators of Non-cell Autonomous Intercellular Communication in Senescence via the Interferon Protein IFITM3.
Disease, Subject
View SamplesGene expression changes in 3 human melanoma cell lines were compared to freshly isolated normal primary melanocytes Overall design: Three biological replicates for each melanoma cell line and primary melanocytes were labeled and run Illumina HiSeq2500. The transcriptome of melanocytes was compared to cell line SK-Mel-28, SK-Mel-147 or UACC-62.
Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1.
Specimen part, Subject
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