Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mouse models to investigate in situ cell fate decisions induced by TP53 and other factors (CUT&RUN)

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE243999 | GEO | 2024/06/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Combined absence of Trp53 target genes Zmat3, Puma and p21 cause a high incidence of cancer in mice

Project description:Transcriptional activation of target genes is essential for TP53-mediated tumour suppression, though the roles of the diverse TP53-activated target genes in tumour suppression remains poorly understood. Knockdown of Zmat3, an RNA-binding zinc-finger protein involved in regulating alternative splicing, in haematopoietic cells by shRNA caused leukaemia only with the concomitant absence of the Puma and p21, the critical effectors of Trp53-mediated apoptosis and cell cycle arrest respectively. We were interested to further investigate the role of ZMAT3 in tumour suppression beyond the haematopoietic system. Therefore, we generated Zmat3 knockout and compound gene knockout mice, lacking Zmat3 and p21, Zmat3 and Puma or all three genes. Puma-/-p21-/-Zmat3-/- triple knockout mice developed tumours at a significantly higher frequency compared to wild-type, Puma-/-Zmat3-/- or p21-/-Zmat3-/-deficient mice. Interestingly, we observed that the triple knockout and Puma-/-Zmat3-/- double deficient animals succumbed to lymphoma, while p21-/-Zmat3-/- animals developed mainly solid cancers. This analysis suggests that in addition to ZMAT3 loss, additional TRP53-regulated processes must be disabled simultaneously for TRP53-mediated tumour suppression to fail. Our findings reveal that the absence of different TRP53 regulated tumour suppressive processes changes the tumour spectrum, indicating that different TRP53 tumour suppressive pathways are more critical in different tissues.

2023-11-28 | GSE248747 | GEO

Repression of p53-target gene Bbc3/puma by MYSM1 is essential for the survival of hematopoietic multipotent progenitors and contributes to stem cell maintenance

Project description:MYSM1 is a transcriptional regulator essential for HSC function and hematopoiesis. We established that p53 activation is a common mechanism mediating HSC dysfunction, MPP depletion, and lymphopenia in Mysm1-deficiency, however, the specific p53-induced effectors that trigger dysfunction in Mysm1-deficient HSPCs remain unknown. Here, we performed RNA-Seq of Lin-cKit+Sca1+CD150+ and CD150- HSPCs from Mysm1-/-Puma-/-, Mysm1-/-Puma+/-, Puma-/-, and wild-type mice; (Mysm1-/-Puma+/- phenocopies Mysm1-/-). We showed that Bbc3/PUMA is the primary non-redundant mediator of MPP depletion in Mysm1-deficiency and contributes to HSC dysfunction, whereas depletion of lymphoid-lineage cells involves PUMA-independent p53 activities. We also identified a broad downregulation of genes encoding protein components of the ribosome (RP-genes) and other regulators of translation in Mysm1-deficiency, and the downregulation persisted in Mysm1-/-Puma-/-.

2020-07-22 | GSE150665 | GEO

Transcriptome of IL-19 negative and IL-19 positive macrophages.

Project description:RNA-seq analysis of LPS stimulated bone marrow-derived macrophages, derived from heterozygous Il19-tdTomato reporter mice to compare the transcritptome of IL-19/tdTomato negative with IL-19/tdTomato positive macrophages.

2017-08-07 | GSE94939 | GEO

Whole transcriptome analysis of FACS purified somatosensory neuron subtypes and whole dorsal root ganglia tissue

Project description:The goal of this study was to analyze global gene expression in specific populations of somatosensory neurons in the periphery, including major, non-overlapping populations that include nociceptors, pruriceptors, and prorioceptors. The mammalian somatosensory nervous system encodes the perception of specific environmental stimuli. The dorsal root ganglion (DRG) contains distinct somatosensory neuron subtypes that innervate diverse peripheral tissues, mediating the detection of thermal, mechanical, proprioceptive, pruriceptive, and nociceptive stimuli. We purified discrete subtypes of mouse DRG somatosensory neurons by flow cytometry using fluorescently labeled mouse lines (SNS-Cre/TdTomato, Parv-Cre/TdTomato) in combination with Isolectin B4-FITC surface staining (IB4). This allowed identification of transcriptional differences between these major populations, revealing enrichment of voltage-gated ion channels, TRP channels, G-protein coupled receptors, transcription factors, and other functionally important classes of genes within specific somatosensory neuron subsets. SNS-Cre mice were bred with Rosa26-TdTomato mice to generate SNS-Cre/TdTomato reporter mice. Parv-Cre mice were bred with Rosa26-TdTomato mice to generate Parv-Cre/TdTomato mice. Isolectin B4-FITC was used to stain the surface of SNS-Cre/TdTomato reporter mice. We used these strategies of fluorescent labeling to purify distinct murine sensory neuron subsets from the dorsal root ganglia (DRG) by fluorescence activated cell sorting (FACS). Neurons were sorted directly in Qiazol for total RNA extraction and microarray analysis. Whole DRG tissue was also included for transcriptome analysis to compare with purified neuronal populations.

2014-12-23 | E-GEOD-55114 | biostudies-arrayexpress

RNA-seq profiles of Tp53, Prkar1a and Axin1 edited basal organoids from a mouse model of breast cancer

Project description:This study demonstrates the applicability of an in vivo CRISPR/Cas9 genome-wide screen in the BALB/c-Trp53+/– mouse model of breast cancer to identify novel tumor suppressor genes involved in mammary tumorigenesis. Preneoplastic mammary organoids were established from using sorted basal cells isolated from BALB/c-Trp53+/– mice. CRISPR/Cas9 screening was used to target Trp53, Axin1 and Prkar1a. To explore the potential molecular basis of the morphological differences, RNA-seq analysis was used to compare the Axin1/Trp53 and Prkar1a/Trp53-edited organoids and to organoids targeted by Trp53-only guides.

2021-12-21 | GSE184070 | GEO

Eed, a member of the Polycomb group, is required for nephron differentiation and the maintenance of nephron progenitor cells

Project description:We used R26R-tdTomato reporter mice activated by the Six2-TGC transgene to isolate cell populations co-expressing GFP and tdTomato by FACS from kidneys of control P0 mice. We observed two distinct populations of cells from control kidneys based on lower or higher tdTomato expression along with high GFP-expression from the Six2-TGC transgene. RNASeq experiment was conducted to analyze the transcriptome of these populations

2018-07-04 | GSE102690 | GEO

Transcriptional Response to transgenic BRAF(V600K) in the intestinal epithelium

Project description:We have analysed transcriptional effects of BRAF(V600K) in the intestinal epithelium of transgenic mice that harbour an inducible BRAF(V600K) transgene. Mice used in this experiment were compound transgenic for a stem-cell specific Lgr5-EGFP Reporter and either an inducible TdTomato-2A-BRAF(V600K) transgene or an inducibe TdTomato-luciferase transgene.

2013-12-31 | GSE50678 | GEO

Transcriptional Idenetity of Itch-activated Central Amygdala Neurons

Project description:We performed RNA-seq to identify transcriptional profiles of itch-activated CeA neurons. To do this, we crossed FosTRAP mice to the Cre-dependent tdTomato flox-stop reporter line as described above. We then injected chloroquine into the nape of the neck, paired with injection of 4-OHT to FosTRAP expression of tdTomato in itch-activated neurons. The CeA was harvested, the cells dissociated and sorted by FACS, and tdTomato+ cells were compared to TdTomato- cells.

2020-04-23 | GSE130268 | GEO

RNA-seq of Smarca5-deficient CD4/CD8 double-positive thymocytes isolated from 6-week mouse thymi and their comparison with wild-type and TP53-null controls.

Project description:Here we utilized a conditional knock-out mouse model to investigate the role of Smarca5, an ISWI subfamily chromatin remodeling ATPase, during thymocyte development using hCD2-iCre transgene. We did transcriptional profiling of FACS-sorted CD4/CD8 double-positive thymocytes as this thymic population was persistent yet strongly underrepresented in adult 6-week mutant thymi. Controls included age-matched CD4/CD8 double-positive thymocytes from wild-type and tumor suppressor protein Trp53-null mice. For comparison, the Smarca5/Trp53-double-deficient thymocytes included in the experiment were partially rescued upon loss of Trp53.

2019-04-01 | E-MTAB-7758 | biostudies-arrayexpress

CRISPR screen to identify regulators of epigenetic memory in ESC

Project description:A genome-wide CRISPR screen was combined with a tdTomato reporter-based epigenetic memory assay to identify factors that erase epigenetic memory in ESC. After introducing genome wide perturbation and dCas9::KRAB-mediated epigenetic editing of the Esg1-tdTomato reporter, the trigger was released and cells that maintained the silencing sorted at FACS. Samples were collected out of sorted tdTomato negative (TOMminus) and positive (TOMplus) cells after 6 days of DOX treatment (epigenetic editing) and 3 or 7 days of DOX washout (release of the trigger), using a gating strategy to separate the bottom 2.5% negative cells (2.5%gate) and cells ranging from mildly to fully repressed (widegate).

2021-11-23 | E-MTAB-10524 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data