Mouse models to investigate in situ cell fate decisions induced by TP53 and other factors (CUT&RUN)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1020858 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26170112_1.fastq.gz | Fastqsanger.gz | |||
| SRR26170112_2.fastq.gz | Fastqsanger.gz | |||
| SRR26170113_1.fastq.gz | Fastqsanger.gz | |||
| SRR26170113_2.fastq.gz | Fastqsanger.gz | |||
| SRR26170114_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 46 |
Similar Datasets
Project description:We developed triple-FLAG TRP53 knock-in mice for TRP53 pull-down and two TRP53 response reporter mice, knocking tdTomato or GFP into the Puma/Bbc3 or p21 gene loci, respectively. By crossing the reporter mice onto a TRP53-deficient background, we could show that these reporters reliably inform on TRP53-dependent and TRP53-independent initiation of the apoptotic as well as the cell cycle arrest/senescence programs in vitro and even in vivo.
2024-06-28 | GSE243999 | GEO
Project description:In order to investigate the potential role of TP53 in regulating translation, HCT116 wild type and TP53 knockout cells were analyzed using both RNA sequencing, Ribosome sequencing and nascent proteome analysis. The cells were treated with 0.2 µg/ml Neocarcinostatin (NCS) to induce DNA damage and activate TP53.
2022-04-27 | PXD029512 | Pride
Project description:Unlike Chromatin Immunoprecipitation (ChIP), which fragments and solubilizes total chromatin, Cut-and-Run is performed in situ, allowing for both high-resolution chromatin mapping and probing of the local chromatin environment. When applied to yeast and human nuclei, Cut-and-Run yielded precise transcription factor profiles while avoiding cross-linking and solubilization issues. Cut-and-Run is simple to perform and at low temperatures is inherently robust, with extremely low backgrounds that make it especially cost-effective for transcription factor and chromatin profiling. When used in conjunction with native ChIP-seq and applied to human CTCF, Cut-and-Run mapped high-resolution 3D directional interactions. We conclude that Cut- and-Run is a suitable complement or replacement for ChIP-seq that can also provide 3D mapping information.
2016-12-30 | GSE84474 | GEO
Project description:Co-existing TP53 and ARID1A mutations promote aggressive endometrial tumorigenesis [CUT&RUN]
| PRJNA764783 | ENA
Project description:The adaptor protein LNK (SH2B3) has emerged as an important protein in regulating B cell development B cell leukemia. Loss-of-function mutations in LNK (SH2B3) are found in Philadelphia chromosomeâlike acute lymphoblastic leukemia (Ph-like ALL), but how LNK regulates normal B cell development or promotes leukemogenesis remains unclear. We found that combined loss of Lnk and tumor suppressors Tp53 in mice triggers a highly aggressive and transplantable precursor B-ALL. This study aims to investigate the molecular mechanism by which LNK regulates B-ALL development. We performed expression profiling of bone marrow proB progenitors from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. Results suggest that Tp53-/-Lnk-/- B-ALLs display similar gene expression profiles to human Ph-like B-ALLs, suggesting this model for preclinical and molecular studies. B220+CD19+CD43+AA4.1+IgM-NK1.1-Ly6c- bone marrow proB cells were double sorted from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. RNA was isolated using miRNeasy kit from QIAGEN and processed using the NuGEN Pico kit. The microarray analysis was performed at the PENN Molecular Profiling/Genomics Facility using GeneChip Mouse Gene 2.0ST array (Affymetrix).
2016-04-01 | E-GEOD-76940 | biostudies-arrayexpress
Project description:TP53 and ARID1A are frequently mutated across cancer but rarely in the same primary tumor. Endometrial cancer has the highest TP53-ARID1A mutual exclusivity rate. However, the functional relationship between TP53 and ARID1A mutations in the endometrium has not been elucidated. We used genetically engineered mice and in vivo genomic approaches to discern both unique and overlapping roles of TP53 and ARID1A in the endometrium. TP53 loss with oncogenic PIK3CA*H1047R in the endometrial epithelium results in features of endometrial hyperplasia, adenocarcinoma, and intraepithelial carcinoma. Mutant endometrial epithelial cells were transcriptome profiled and compared to control cells and ARID1A/PIK3CA mutant endometrium. In the context of either TP53 or ARID1A loss, PIK3CA mutant endometrium exhibited inflammatory pathway activation, but other gene expression programs differed based on TP53 or ARID1A status, such as epithelial-to-mesenchymal transition. Gene expression patterns observed in the genetic mouse models are reflective of human tumors with each respective genetic alteration. Consistent with TP53-ARID1A mutual exclusivity, the p53 pathway is activated following ARID1A loss in the endometrial epithelium, where ARID1A normally directly represses p53 pathway genes in vivo, including the stress-inducible transcription factor, ATF3. However, co-existing TP53-ARID1A mutations led to invasive adenocarcinoma associated with mutant ARID1A-driven ATF3 induction, reduced apoptosis, TP63+ squamous differentiation and invasion. These data suggest TP53 and ARID1A mutations drive shared and distinct tumorigenic programs in the endometrium and promote invasive endometrial cancer when existing simultaneously. Hence, TP53 and ARID1A mutations may co-occur in a subset of aggressive or metastatic endometrial cancers, with ARID1A loss promoting squamous differentiation and the acquisition of invasive properties.
2021-12-13 | GSE184498 | GEO
Project description:Investigating how transcription factors control complex cellular processes requires tools that enable responses to be visualised at the single-cell level and their cell fate to be followed over time. For example, the tumour suppressor p53 (also called TP53 in humans and TRP53 in mice) can initiate diverse cellular responses by transcriptional activation of its target genes: Puma to induce apoptotic cell death and p21 to induce cell cycle arrest/cell senescence. However, it is not known how these processes are regulated and initiated in different cell types. Also, the context-dependent interaction partners and binding loci of p53 remain largely elusive. To be able to examine these questions, we here developed knock-in mice expressing triple-FLAG-tagged p53 to facilitate p53 pull-down and two p53 response reporter mice, knocking tdTomato and GFP into the Puma/Bbc3 and p21 gene loci, respectively. By crossing these reporter mice into a p53-deficient background, we show that the new reporters reliably inform on p53-dependent and p53-independent initiation of both apoptotic or cell cycle arrest/senescence programs, respectively, in vitro and in vivo.
| S-SCDT-10_1038-S44318-024-00189-Z | biostudies-other
Project description:DNA damage activates diverse cellular responses – either protective or deleterious –that ultimately promote or inhibit proliferation. How the distinct responses conferring crucial cell fate decisions are chosen is unclear. Using a systems approach, we demonstrate that the dynamic features of Atm dependent DNA double-strand break (DSB) signalling response dictate cellular outcome. Combining temporal phosphoproteome and nascent transcriptome analyses after low or high DNA-damage-load, we discovered that some responses, such as Tp53 activation, have an activation threshold and others arise independently of DNA-damage-load. Using DSB repair deficient cells, we show that persistent DSBs alter the kinetics – but not the amplitude – of Atm signalling. Thus, we demonstrate that pathway choices are dictated by the signalling dynamics and hence cell fate decisions are responsive to DNA-damage-load and repair capacity of the cells.
2023-01-18 | PXD013620 | Pride
Project description:The adaptor protein LNK (SH2B3) has emerged as an important protein in regulating B cell development B cell leukemia. Loss-of-function mutations in LNK (SH2B3) are found in Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL), but how LNK regulates normal B cell development or promotes leukemogenesis remains unclear. We found that combined loss of Lnk and tumor suppressors Tp53 in mice triggers a highly aggressive and transplantable precursor B-ALL. This study aims to investigate the molecular mechanism by which LNK regulates B-ALL development. We performed expression profiling of bone marrow proB progenitors from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. Results suggest that Tp53-/-Lnk-/- B-ALLs display similar gene expression profiles to human Ph-like B-ALLs, suggesting this model for preclinical and molecular studies.
2016-04-01 | GSE76940 | GEO