Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The C-terminus of p53 Confers Liver-Specific Gene Regulation and Radio-Resistance in vivo [RNA-Seq]

ABSTRACT: Thymus and spleen, in contrast to liver, are radiosensitive tissues in which p53-dependent apoptosis is triggered after whole body radiation in vivo. Combined RNA-seq and ChIP-seq analyses of radiation-treated mouse organs identifies both shared and tissue-specific p53 transcriptional responses. As expected, the p53 targets shared amongst thymus and spleen are enriched in apoptotic targets. Surprisingly, the inability to upregulate these genes in the liver is not due to reduced gene occupancy. Use of an engineered mouse model shows that deletion of the C-terminus of p53 can confer radiation-induced expression of p53 apoptotic targets in the liver with concomitant increased cell death. Global RNA-seq analysis reveals an additional role of the C-terminus being also needed for transcriptional activation of liver-specific p53 targets. It is hypothesized that both suppression of apoptotic gene expression combined with enhanced activation of liver-specific targets confers tissue-specific radio-resistance.

ORGANISM(S): Mus musculus

PROVIDER: GSE204924 | GEO | 2022/06/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The C-terminus of p53 Confers Liver-Specific Gene Regulation and Radio-Resistance in vivo [ChIP-seq]

Project description:Thymus and spleen, in contrast to liver, are radiosensitive tissues in which p53-dependent apoptosis is triggered after whole body radiation in vivo. Combined RNA-seq and ChIP-seq analyses of radiation-treated mouse organs identifies both shared and tissue-specific p53 transcriptional responses. As expected, the p53 targets shared amongst thymus and spleen are enriched in apoptotic targets. Surprisingly, the inability to upregulate these genes in the liver is not due to reduced gene occupancy. Use of an engineered mouse model shows that deletion of the C-terminus of p53 can confer radiation-induced expression of p53 apoptotic targets in the liver with concomitant increased cell death. Global RNA-seq analysis reveals an additional role of the C-terminus being also needed for transcriptional activation of liver-specific p53 targets. It is hypothesized that both suppression of apoptotic gene expression combined with enhanced activation of liver-specific targets confers tissue-specific radio-resistance.

2022-06-30 | GSE203643 | GEO

Extracts from sweet sorghum (Sorghum bicolor), a feedstock for biorefining, suppressed proliferation and elevated apoptosis in human colon cancer stem cells via suppression of Wnt/beta-catenin signaling pathway

Project description:In colorectal cancer, p53 is commonly inactivated, associated with chemo-resistance, and marks the transition from non-invasive to invasive disease. Cancers, including colorectal cancer, are thought to be diseases of aberrant stem cell populations, as stem cells are able to self-renew, making them long-lived enough to acquire mutations necessary to manifest the disease. We have shown that extracts from sweet sorghum stalk components eliminate colon cancer stem cells (CCSC) in a partial p53-dependent fashion. However, the underlying mechanisms are unknown. In the present study, CCSC were transfected with short hairpin-RNA against p53 (CCSC p53 shRNA) and treated with sweet sorghum phenolics extracted from different plant components (dermal layer, leaf, seed head and whole plant). While all components demonstrated anti-proliferative and pro-apoptotic effects in CCSC, phenolics extracted from the dermal layer and seed head were more potent in eliminating CCSC by elevating caspases 3/7 activity, PARP cleavage, and DNA fragmentation in a p53-dependent and p53-independent fashion, respectively. Further investigations revealed that the anti-proliferative and pro-apoptotic effects were associated with decreases in beta-catenin protein levels, and beta-catenin targets cyclin D1, cMyc, and survivin. These results suggest that the anti-proliferative and pro-apoptotic effects of sweet sorghum extracts against human colon cancer stem cells are via suppression of Wnt/beta-catenin pro-survival signaling in a p53-dependent (dermal layer) and partial p53-independent (seed head) fashion. LCMS used to identify phenolic compounds associated with extract activity

2014-05-01 | MTBLS69 | MetaboLights

Exploring the organ specific expression pattern of CD4+iNKT1 cells of C57BL/6 and BALB/c mice.

Project description:iNKT cells are generated in thymus and settle all organs and tissues in mice. We used RNA high throughput sequencing to identify genes that displayed an organ specific expression by comparing iNKT1 cells of thymus, liver, blood, and spleen origin, respectively. We observed organ specific expression of a variety of genes that might reflect specialized functional adaptations connected to the unique micro-environments of the investigated organs.

2021-11-18 | GSE160144 | GEO

Type 1 immunity enables neonatal thymic ILC1 production

Project description:We used scRNA seq to analyze mice organ cells (liver, spleen, thymus and bone marrow) as well as neonatal thymus organ cultures that were treated cytokines IL-12 and IL-18.

2024-03-04 | GSE229632 | GEO

Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo [ChIP-Seq]

Project description:The tumor suppressor p53 is a transcription factor that coordinates the cellular response to DNA damage. Here we provide an integrated analysis of p53 genomic occupancy and p53-dependent gene regulation in the splenic B and non-B cell compartments of mice exposed to whole-body ionizing radiation, providing insight into general principles of p53 activity in vivo. In unstressed conditions, p53 bound few genomic targets; induction of p53 by ionizing radiation increased the number of p53 bound sites, leading to highly overlapping profiles in the different cell types. Comparison of these profiles with chromatin features in unstressed B cells revealed that, upon activation, p53 localized at active promoters, distal enhancers, and a smaller set of unmarked distal regions. At promoters, recognition of the canonical p53 motif as well as binding strength were associated with p53-dependent transcriptional activation, but not repression, indicating that the latter was most likely indirect. p53-activated targets constituted the core of a cell type-independent response, superimposed onto a cell type-specific program. Core response genes included most of the known p53-regulated genes, as well as many new ones. Our data represent a unique characterization of the p53-regulated response to ionizing radiation in vivo. Mapping p53 binding sites in the splenic B and non-B cell compartments of mice exposed to whole-body ionizing radiation

2015-08-24 | E-GEOD-71175 | biostudies-arrayexpress

Human SMARCA5 interactome in transgenic SMARCA5 mouse model

Project description:We hypothesize that the ISWI ATPase Smarca5 plays a role in hematopoietic stem cell development via its interaction partners, and to study the role, we used a mouse model with transgenic expression of SMARCA5 coupled with mass spectrometry analysis. The study uses transgenic SMARCA5 mouse model with conditional hypomorphic allele (lower expression on protein level compared to controls) incorporated into Rosa26 locus, transgenic allele uses endogenous Rosa26 promoter. The transgenic human SMARCA5 protein has a FLAG tag at its C-terminus, which allows specific immunoprecipitation and also differentiation from the endogenous protein (human and mouse SMARCA5 are almost identical at the protein level). To ensure the highest possible expression of the transgenic allele, we used a model that also had one endogenous Smarca5 allele deleted. Various organs (thymus, spleen, brain, kidney, liver, testes, muscle, fetal liver) were isolated from transgenic mice, lysed and then immunoprecipitated using anti-FLAG antibody. The immunoprecipitates were then analyzed using mass spectrometry to determine SMARCA5 interactomes in various tissues. Transgenic human SMARCA5 was confirmed to form all the expected complexes and capable of replacing the functions of the mouse protein. For details, see the publication of Turkova et al. 2024 in Communications Biology.

2024-06-22 | PXD049034 | Pride

Transcriptomics coupled proteomics reveals the critical signaling pathways regulating OVA antigen-specific CD8+ T cells in mouse spleen and liver

Project description:Background: Antigen-specific T cells are particularly important for eliminating bacterial infection, and the dynamics in this process help uncover the mechanisms by which bacteria are eliminated.Results: In this study, we sorted the antigen-specific CD8+ T cell in the mouse liver and spleen at 5, 7, and 14 days after infection of Listeria monocytogenes expressing the OVA protein, finding that antigen-specific CD8+ T cell expansion after infection peaked on Day 7. Through the RNAseq analysis, we identified 355 genes whose expression peaked on 7 days post-infection shared in both of spleen and liver. For these shared genes, the KEGG pathway analysis showed a notable enrichment in the metabolic pathway. We also discovered 1621 proteins shared in the mouse liver and spleen that peaked seven days after infection by the LC-MS/MS analysis. The KEGG pathway analysis for these proteins revealed a significant enrichment in Splicesome, RNA transport, Ubiquitin mediated proteolysis, and Huntington disease. Transcriptomics coupled proteomics reveals 45 genes/proteins that were elevated on day 7 post listeria infection both in the spleen and liver. These 45 molecules were enriched in Human T-cell leukemia virus 1 infection and T cell activation, which played an important role in the activation of T cells and the anti-infection process.Conclusion: Transcriptomics coupled proteomics reveals the key signaling pathways to regulate antigen-specific CD8+ T cells by infection of Listeria monocytogenes expressing the OVA protein in mouse spleen and liver.

2024-04-10 | GSE263368 | GEO

Identification of age-related changes in gene expression and chromatin accessibility in T cells from thymus to periphery (60K)

Project description:Aging of immune system is characterized by progressive decline of physiological and cellular function of T cells. Recent studies of naïve T cells from young and old mice have identified age-related altered gene expressions but the mechanisms underlying age associated changes of naïve T cells remain poorly understood. Here we compared the transcriptome and chromatin accessibility in mature CD4 and CD8 thymocytes and in naïve CD4 and CD8 T cells of spleen between young (6-8 weeks) and old (79-121 weeks) C57Bl/6 mice. We used Agilent microarray method and identified the age-related altering gene expressions 1) only in mature CD4 and CD8 T cell from thymus, 2) shared by both thymus and spleen naïve T cells, and 3) only in naïve T cells from spleen. The shared changes include increased chemokine and chemokine receptor expressions and decreased cell cycle regulator expression. We further analyzed the chromatin basis of altered gene expression using Assaying Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) between young and old mice. We have identified age-related changes of chromatin accessibility in T cells from thymus and spleen, and some correlated changes between gene expression and chromatin accessibility. Overall, we observedmore age-related alterations of gene expression and chromatin accessibility inthymus than in spleen, suggesting some age-related changes of T cells in thymus did not retain in periphery. Together, our findings have identified tissue specific altered gene expressions and chromatin status in T cells during aging and further study of these altered genes will shed new insights into the mechanisms underlying these age-related changes.

2021-03-19 | GSE112391 | GEO

Identification of age-related changes in gene expression and chromatin accessibility in T cells from thymus to periphery (44K)

2021-03-19 | GSE112390 | GEO

Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo [DNAse-Seq]

2015-08-24 | E-GEOD-71177 | biostudies-arrayexpress