Project description:we report the effect of Ramoplanin on the transcription profile of RPE cells in comparison to DMSO (Vehicle) or MFGE8+GAS6 treated cells in the presence and absence of POS
Project description:T-cell-specific deletion of USP8 (USP8ffCD4Cre) revealed that USP8 is required for thymocyte transition to the CD4+ and CD8+ single positive (SP) stages. To evaluate underlying mechanisms, gene expression profilling was performed in CD4+CD8+ double pos thymocytes derived from control (USP8ff and USP8ffCD4Cre) mice.
Project description:T-cell-specific deletion of USP8 (USP8ffCD4Cre) revealed that USP8 is required for thymocyte transition to the CD4+ and CD8+ single positive (SP) stages. To evaluate underlying mechanisms, gene expression profilling was performed in CD4+CD8+ double pos thymocytes derived from control (USP8ff and USP8ffCD4Cre) mice. Microarray analysis of two groups of USP8fl/fl and USP8fl/flCD4Cre thymocytes. Material from two mice was combined for each group (eight mice in total).
Project description:The role of cells expressing stem cell markers deltaNp63 and CD44v has not yet been elucidated in peripheral-type lung squamous cell carcinoma (pLSCC) carcinogenesis. Female A/J mice were painted topically with N-nitroso-tris-chloroethylurea (NTCU) for induction of pLSCC, and the histopathological and molecular characteristics of NTCU-induced lung lesions were examined. Histopathologically, we found atypical bronchiolar hyperplasia, squamous metaplasia, squamous dysplasia, and pLSCCs in the treated mice. Furthermore, we identified deltaNp63(pos)CD44v(pos)CK5/6(pos)CC10(pos) clara cells as key constituents of early precancerous atypical bronchiolar hyperplasia. In addition, deltaNp63(pos)CD44v(pos) cells existed throughout the atypical bronchiolar hyperplasias, squamous metaplasias, squamous dysplasias, and pLSCCs. Overall, our findings suggest that NTCU induces pLSCC through an atypical bronchiolar hyperplasia-metaplasia-dysplasia-SCC sequence in mouse lung bronchioles. Notably, Ki67-positive deltaNp63(pos)CD44v(pos) cancer cells, cancer cells overexpressing phosphorylated epidermal growth factor receptor and signal transducer and activator of transcription 3, and tumor-associated macrophages were all present in far greater numbers in the peripheral area of the pLSCCs compared with the central area. These findings suggest that deltaNp63(pos)CD44v(pos) clara cells in mouse lung bronchioles might be the origin of the NTCU-induced pLSCCs. Our findings also suggest that tumor-associated macrophages may contribute to creating a tumor microenvironment in the peripheral area of pLSCCs that allows deltaNp63(pos)CD44v(pos) cancer cell expansion through activation of epidermal growth factor receptor signaling, and that exerts an immunosuppressive effect through activation of signal transducer and activator of transcription 3 signaling.
Project description:<p><strong>INTRODUCTION:</strong> The absolute quantitation of lipids at the lipidome-wide scale is a challenge but plays an important role in the comprehensive study of lipid metabolism. </p><p><strong>OBJECTIVES:</strong> We aim to develop a high-throughput quantitative lipidomics approach to enable the simultaneous identification and absolute quantification of hundreds of lipids in a single experiment. Then, we will systematically characterize lipidome-wide changes in the aging mouse brain and provide a link between aging and disordered lipid homeostasis. </p><p><strong>METHODS:</strong> We created an in-house lipid spectral library, containing 76,361 lipids and 181,300 MS/MS spectra in total, to support accurate lipid identification. Then, we developed a response factor-based approach for the large-scale absolute quantifications of lipids. </p><p><strong>RESULTS:</strong> Using the lipidomics approach, we absolutely quantified 1212 and 864 lipids in human cells and mouse brains, respectively. The quantification accuracy was validated using the traditional approach with a median relative error of 12.6%. We further characterized the lipidome-wide changes in aging mouse brains, and dramatic changes were observed in both glycerophospholipids and sphingolipids. Sphingolipids with longer acyl chains tend to accumulate in aging brains. Membrane-esterified fatty acids demonstrated diverse changes with aging, while most polyunsaturated fatty acids consistently decreased. </p><p><strong>CONCLUSION:</strong> We developed a high-throughput quantitative lipidomics approach and systematically characterized the lipidome-wide changes in aging mouse brains. The results proved a link between aging and disordered lipid homeostasis. </p><p><br></p><p><strong>Mouse brain POS UPLC-MS assay</strong> data is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS562' rel='noopener noreferrer' target='_blank'><strong>MTBLS562</strong></a>. </p><p><strong>Mouse brain NEG UPLC-MS assay</strong> data associated to this study is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS495' rel='noopener noreferrer' target='_blank'><strong>MTBLS495</strong></a>.</p>