The impact of the Trp53 allelic state on the response to gamma-irradiation in hematopoietic stem and progenitor cells
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PROVIDER: PRJNA1309689 | ENA |
REPOSITORIES: ENA
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Project description:We investigated how the Trp53 allelic state influences the response of hematopoietic stem and progenitor cells (HSPCs) to γ-irradiation. We used a transgenic mouse model harboring hematopoietic cell–specific, tamoxifen-inducible Trp53-R245W missense mutations linked to a GFP reporter. In mice with biallelic transgenes, tamoxifen treatment generates three GFP-defined populations: GFP-negative cells (Trp53 wild-type), GFP-low cells (monoallelic Trp53 mutation, due to recombination of only one transgenic allele), and GFP-high cells (biallelic Trp53 mutation). Flow sorting of these populations enables direct comparison of all three allelic states in HSPCs. Using this system, we sought to define the transcriptional responses of HSPCs with different Trp53 genotypes following γ-irradiation.
2025-08-26 | GSE306213 | GEO
Project description:Trp53-null, Trp53-515C/515C (encoding p53R172P), or wild-type mouse embryo fibroblasts were treated with 6 Gy gamma-radiation and harvested 6 hours later to compare expression profiles of genes regulated by wild-type p53 and p53R172P. Trp53-null cells were included as a negative control.
2006-11-20 | E-MEXP-917 | biostudies-arrayexpress
Project description:Trp53 is an essential tumor suppressor gene that coordinates the response to cellular stress, including exposure to chemotherapeutic agents. We aimed to characterize the effect of various Trp53 allelic states (i.e. wild-type, monoallelic mutations and biallelic mutations) on the modulation of downstream pathways in the context of treatment with the chemotherapeutic agent etoposide. In order to obtain a cell model that represents key characteristics of the pre-malignant condition of clonal hematopoiesis, we utilized ER-Hoxb8 cells, which represent an immortalized, but otherwise genetically normal hematopoietic progenitor cell line. Generation of this cell model from a mouse strain carrying the inducible Trp53 missense mutation R245W in the endogenous locus and coupled to a GFP reporter, allows therefore to study the impact of the various allelic states of Trp53 on cellular consequences in a context that models clonal hematopoiesis.
2025-06-17 | GSE299918 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE10858: Comparative Genomic hybridization of gamma-irradiated T-cell lymphomas GSE10859: Expression patterns of cDNAs in gamma-irradiation induced T-cell lymphomas GSE10891: Gamma-irradiation induced T-cell lymphomas (miRNA study) Keywords: SuperSeries Refer to individual Series
2010-05-26 | E-GEOD-10861 | biostudies-arrayexpress
Project description:Our group previously demonstrated that the Trp53 R270H mutation can drive prostate cancer (CaP) initiation in a genetically engineered mouse model (FVB.129S4(Trp53tm3Tyj/wt);FVB.129S(Nkx3-1tm3(cre)Mmswt)). The objective of the current study was to identify molecules that may facilitate Trp53 R270H-mediated prostate carcinogenesis. Mice that harbor a Trp53 R270H germline mutation (B6.129S4-Trp53tm3.1Tyj/J) were used for the current study. Wildtype (Trp53WT/WT), heterozygous (Trp53R270H/WT), and homozygous mice (Trp53R270H/R270H) were exposed to 5 Gy radiation to activate and stabilize p53 and thereby enhance our ability to identify differences in transcriptional activity between the 3 groups of mice. Mouse prostates were harvested 6 hours post-irradiation and either processed for histological/immunohistochemistry (IHC) analysis or snap-frozen for RNA extraction and transcriptome profiling with RNA-Sequencing (RNA-Seq) analysis. IHC was used to assess cell proliferation (Ki67) and apoptosis (activated caspase 3). PIN lesions were observed in heterozygous and homozygous mice as early as 3 months, thereby validating our prior finding that the Trp53 R270H mutation can drive CaP initiation. RNA-Seq analysis identified 1,378 differentially expressed genes, including multiple wildtype p53 target genes (E.g. Cdkn1a, Bax, Bcl2, Kras, Mdm2), p53 gain-of-function (GOF) genes (Mgmt, Id4), and CaP-related genes (Cav-1, Raf1, Kras). Our combined data validate a role for the Trp53 R270H mutation in CaP initiation, and identify molecules that may contribute to Trp53 R270H-mediated prostate carcinogenesis.
2022-03-02 | GSE130440 | GEO
Project description:We established a mouse model to study the development of therapy-related myeloid neoplasms (t-MN) arising from TP53-mutant clonal hematopoiesis. Mice carrying conditional Trp53-fl-R245W-GFP alleles, in combination with the inducible hematopoietic-specific Cre driver (SCL-CreERT), allow induction of either monoallelic or biallelic Trp53 missense mutations. To mimic cytotoxic therapies implicated in t-MN pathogenesis, mice were exposed to sublethal γ-irradiation, which promoted the development of hematologic malignancies, including acute erythroid leukemia. We then subjected these leukemias to bulk RNA sequencing to characterize their transcriptomic landscape.
2025-08-26 | GSE306212 | GEO
Project description:Transcriptome alterations in prostates from Trp53 R270H mutant mice following irradiation
| PRJNA540264 | ENA
Project description:Arabidopsis cmt3 mutant showed neither DNA hypomethylation nor transcriptional activation of silenced repeats by gamma rays, which was found in wild type (WT). We used microarrays to compare the global transcriptional changes between the WT and cmt3 after the irradiation of 200 Gy. Transcriptions of transposition-related genes seemed to be differently affected in the WT and cmt3 by gamma rays, depending on the epigenetic codes of the genome. However, genome-wide transcriptions of the WT and cmt3 couldn't be positively correlated with the different levels of DNA methylation after the irradiation of 200 Gy. Rosette leaves from more than 10 plants were pooled for total RNA extraction and hybridization on Affymetrix Arabidopsis ATH1 genechips. We performed two independent array experiments using totally different biological replicates of WT and cmt3 mutant plants with or without gamma irradiation.
2013-06-01 | E-GEOD-43947 | biostudies-arrayexpress
Project description:To check gene expression signatures for LGR5hi and LGR5lo ISCs in response to gamma-irradiation, we performed whole genome microarray on LGR5hi and LGR5lo ISCs purified from irradiated mice or non-irradiated mice Radiation induced gene expression in LGR5hi and LGR5lo ISCs of LGR5-GFPki mice was measured at 3 hours after exposure to 12Gy γ-irradiation or non-irradiation.
2013-08-01 | E-GEOD-49461 | biostudies-arrayexpress
Project description:NK-92 cells and their CAR-modified derivatives exhibit strong cytotoxic activity against tumors and are promising "off-the-shelf" therapeutics compared to CAR-T cells. In order to ensure safety and prevent the occurrence of secondary tumors, (CAR-)NK-92 cells need to be inactivated before transfusion. With increasing clinical use, there is a growing demand for enhanced safety and an efficient method that stops cell proliferation, but better maintains the cytotoxic effector functions of the cells compared to commonly used gamma irradiation. Recently, low-energy electron irradiation (LEEI) was successfully applied for inactivation of bacteria and viruses for vaccine production, and was described as a method for NK-92 inactivation for the first time. In the present publication, data on extensive characterization of LEEI and its comparison with gamma irradiation for the inactivation of parental NK-92 cells as well as CD123-directed CAR-NK-92 cells are provided. Our results show that both irradiation methods cause a progressive decrease in cell viability and are therefore suitable for inhibition of proliferation. Notably, cytotoxicity of the NK cells was significantly reduced by gamma irradiation, but not by LEEI three days after irradiation, compared to non-irradiated cells. Both gamma irradiation as well as LEEI led to substantial DNA-damage and an accumulation of irradiated cells in the G2/M phase. In addition, transcriptomic analysis of cells irradiated with both methods revealed approximately 12-fold more differentially expressed genes after gamma irradiation compared to LEEI. Analysis of surface molecules revealed an irradiation-induced decrease in CD56 expression but no changes in the levels of the activating receptors NKp46, NKG2D, and NKp30. Conclusions: The present data show that LEEI efficiently inactivates (CAR )NK-92 cells and sustains their cytotoxic capacity better than gamma irradiation. Taking into account additional logistic advantages of LEEI proves a potent alternative in the manufacturing of (CAR-)NK-92 cells for clinical application.
2021-05-17 | GSE166976 | GEO