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Transcriptome profiling reveals novel Disabled-2-associated downstream effectors in mouse embryonic stem cells (ESC)

ABSTRACT: Disabled-2 (DAB2) is up-regulated when ESC were cocultured with OP9 stromal cells for mesodermal colony formation. Expression of DAB2 short hairpin small interfering RNA (shDAB2) altered ESC cell-cell adhesion that subsequently affected colony formation and mesoderm differentiation competence. To further unveil the molecular mechanisms associated with the phenotypic change of shDAB2-expressing ES cells, comprehensive profiling of DAB2-regulated molecules in shDAB2-ES cells (ES-V9 and 285-4) were performed by Affimatrix microarray.

ORGANISM(S): Mus musculus

PROVIDER: GSE17592 | GEO | 2009/08/12

SECONDARY ACCESSION(S): PRJNA118499

REPOSITORIES: GEO

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Transcription profiling of mouse embryonic stem cells reveals novel Disabled-2-associated downstream effectors

Project description:Disabled-2 (DAB2) is up-regulated when ESC were cocultured with OP9 stromal cells for mesodermal colony formation. Expression of DAB2 short hairpin small interfering RNA (shDAB2) altered ESC cell-cell adhesion that subsequently affected colony formation and mesoderm differentiation competence. To further unveil the molecular mechanisms associated with the phenotypic change of shDAB2-expressing ES cells, comprehensive profiling of DAB2-regulated molecules in shDAB2-ES cells (ES-V9 and 285-4) were performed by Affimatrix microarray. Experiment Overall Design: Total RNAs from vector control (ES-V9) and shDAB2-expressing (285-4) ESC were isolated by Trizol (Invitrogen) and were further purified using the RNeasy mini kit (Qiagen). For profiling of mRNA expression, the purified total RNAs were then subjected to microarray analysis (Affymetrix gene chip mouse 430A).

2009-08-23 | E-GEOD-17592 | biostudies-arrayexpress

Disabled-2 interacting proteins in U46619-stimulated human platelet activation

Project description:The interacting proteins of Disabled-2 (Dab2) and their functional consequences in U46619-stimulated human platelets were investigated.

2024-10-24 | PXD048490 | Pride

The Disabled homolog 2 controls pro-metastatic activity of tumor-associated macrophages

Project description:Tumor-associated macrophages (TAMs) are regulators of extracellular matrix (ECM) remodeling and metastatic progression, the main cause of cancer-associated death. We found that disabled 2 mitogen-responsive phosphoprotein (DAB2) is highly expressed in tumor-infiltrating TAMs and its genetic ablation significantly impairs lung metastasis formation. DAB2-expressing TAMs, mainly localized along the tumor invasive front, participate in integrin recycling, ECM remodeling and directional migration in a tridimensional matrix. DAB2+ macrophages escort the invasive dissemination of cancer cells by a mechanosensing pathway requiring the transcription factor Yes-Associated Protein. In human lobular breast and gastric carcinomas, DAB2+ TAMs correlated with a poor clinical outcome, identifying DAB2 as potential prognostic biomarker for cancer patient stratification. DAB2 is therefore central for the pro-metastatic activity of TAMs.

2020-07-13 | GSE152674 | GEO

Disabled-2 is a negative immune regulator of lipopolysaccharide-stimulated Toll-like receptor 4 internalization and signaling

Project description:Toll-like receptor 4 (TLR4) plays a pivotal role in the host response to lipopolysaccharide (LPS), a major cell wall component of Gram-negative bacteria. Here we elucidated whether the endocytic adaptor protein Disabled-2 (Dab2) that is abundantly expressed in the macrophages plays a role in LPS-stimulated TLR4 signaling and trafficking. Molecular analysis and transcriptome profiling of the RAW264.7 macrophage-like cells expressing short-hairpin RNA of Dab2 revealed that Dab2 mainly regulated LPS-stimulated TRIF-dependent, but not MyD88-dependent TLR4 signaling. Consequently, knockdown of Dab2 augmented TRIF-dependent interferon regulatory factor 3 activation and the expression for the subsets of inflammatory cytokines and interferon-inducible genes. We further delineated that Dab2 acted as a “clathrin sponge” and sequestered clathrin from TLR4/MD2 complex in the resting stage of macrophages. Clathrin was released from Dab2 and associated with TLR4 to facilitate the internalization of TLR4/MD2 complex together with the bound ligand from the cell surface upon LPS stimulation. Dab2 thereby functions as a negative immune regulator of TLR4 endocytosis and signaling, supporting a novel role of Dab2-associated regulatory circuit in the control of inflammatory response of macrophage to endotoxin.

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Gene expression profile of hair follicle stem cells (HFSCs) isolated from wild type and homozygous Dab2 cKO (Dab2 Fl/Fl) mice at postnatal day 68

Project description:Disabled 2 is an endocytic adaptor protein known to regulate various signaling pathways such Wnt , BMP, TGF and Ras/MAPK. In the present study, we observed that Dab2 is expressed in all the compartments of the hair follicle. K14 Cre specific homozygous Dab2 knockout resulted in delayed activation of HFSCs and delayed Ist hair follicle cycle initiation. At PD68, both WT and Dab2 cKO mice were at telogen. In addition, loss of Dab2 also led to reduced HFSCs pool extended quiescence, and reduced self renewal capacity of HFSCs at PD68. We performed expression profiling of HFSCs isolated from WT and Dab2 cKO mice at PD68 to check for the differentially regulated genes involved in HFSCs activation. The expression analysis helped us to elucidate the detailed molecular mechanisms involved in Dab2 mediated regulation of HFSCs activation and quiescence.

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Gene expression profile of hair follicle stem cells (HFSCs) isolated from wild type and homozygous Dab2 cKO (Dab2 Fl/Fl) mice at postnatal day 35

Project description:Disabled 2 is an endocytic adaptor protein known to regulate various signaling pathways such Wnt , BMP, TGF and Ras/MAPK. In the present study, we observed that Dab2 is expressed in all the compartments of the hair follicle. K14 Cre specific homozygous Dab2 knockout resulted in delayed activation of HFSCs and delayed Ist hair follicle cycle initiation. At PD35, while WT progresses to anagen II, the Dab2 cKO mice still remains at telogen. In addition, loss of Dab2 alos led to reduced HFSCs pool extended quiescence, and reduced self renewal capacity of HFSCs at PD35. We performed expression profiling of HFSCs isolated from WT and Dab2 cKO mice at PD35 to check for the differentially regulated genes involved in HFSCs activation. The expression analysis helped us to elucidate the detailed molecular mechanisms involved in Dab2 mediated regulation of HFSCs activation and quiescence.

2024-03-01 | GSE250300 | GEO

Expression data from SDH-disabled GIST

Project description:Pediatric GIST commonly harbors a disabled succinate dehydrogenase complex (SDH), which yields tumors with highly conserved genomes but characteristic epigenomic signatures. Mysteriously, nearly half of such SDH-deficient GIST, including tumors from Carney Triad patients, lack identifiable mutations in SDH component genes and genes required for complex assembly (SDHA, SDHB, SDHC, SDHD, SDHAF, termed SDHx). Genomic sequencing coupled with DNA methylation and transcriptional profiling have exposed SDHC promoter-specific CpG island epimutation and concomitant gene silencing in the majority of SDHx-WT GIST.

2015-01-02 | GSE56670 | GEO

Estrogen regulated microRNAs in mouse ovarian cancer cells.

Project description:In a mouse model of ovarian cancer, we have established that prolonged exposure to 17β-estradiol (E2) accelerates tumour onset and increases the incidence of morphologically dysplastic ovarian surface epithelium (OSE). OSE cell proliferation and morphology are tightly regulated by the asymmetrical distribution of polarity proteins that provide positional cues for surface localization and growth inhibition. We hypothesized that E2 causes OSE dysplasia by inhibiting a tumour suppressor gene called Disabled-2 (Dab2). Dab2 is critical in mediating the polarized distribution of cell surface proteins and is highly expressed in normal OSE, but is absent in the majority of ovarian cancers. In this study, Dab2 is shown to be suppressed by E2 and we investigated the possibility that this occurs through E2 up-regulation of microRNAs. microRNA microarray analysis comparing control vs. E2 treated mouse ovarian cancer cells (MASE) was used to identify candidate miRNAs that have a seeding sequence capable of targeting the 3-prime untranslated region (3’UTR) of both human and mouse Dab2 transcript.

2017-11-30 | GSE98391 | GEO

Expression data from SDH-disabled GIST

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The Disabled homolog 2 controls pro-metastatic activity of tumor-associated macrophages

Project description:The Disabled homolog 2 controls pro-metastatic activity of tumor-associated macrophages

| PRJNA640048 | ENA