Expression data from a mouse small cell lung cancer (SCLC) cell line, KP1, transfected with Notch-ICD
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE69091 | GEO | 2015/05/21
SECONDARY ACCESSION(S): PRJNA284508
REPOSITORIES: GEO
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Project description:Transient transfection of activated Notch1 (Notch1-ICD) decreases cellular proliferation and reduces the expression of a subset of neuroendocrine genes. We used microarrays to identify the gene expression changes 48 hours after overexpression of Notch1-ICD. mSCLC cells transfected with Notch1-ICD-ires-GFP were FACS sorted for GFP+ cells 48 hours after transfection. RNA was then extracted and hybridized to Affymetrix GeneChip® Mouse Gene 2.0 ST array.
2015-05-21 | E-GEOD-69091 | biostudies-arrayexpress
Project description:We identified histidine triad nucleotide binding protein 1 (HINT1) as a human teneurin-1 ICD interaction partner in a yeast-2 hybrid screen. This interaction was confirmed in human cells, where HINT1 is known to inhibit the transcription of target genes by directly binding to transcription factors at the promoter. In a whole transcriptome analysis of BS149 glioblastoma cells overexpressing the teneurin-1 ICD, several microphthalmia-associated transcription factor (MITF) target genes were found to be up-regulated. Interestingly, MITF is one of the transcription factors inhibited by HINT1. Thus, we directly compare the transcriptomes of MITF versus TEN1-ICD overexpressing BS149 cells in this study, in order to reveal any co-regulated genes. For the whole transcriptome analysis of MITF, cells were transiently transfected in triplicates with either, pcDNA3.1-RFP-HA (negative control) or pcDNA3.1-MITF-RFP-HA. The overexpressing cells were then FACS-sorted directly into RLT lysis buffer (Qiagen) at a 3:1 volume ratio of lysis buffer to cells in PBS, 24 h post-transfection.
2015-02-04 | E-GEOD-61705 | biostudies-arrayexpress
Project description:Teneurins are large type II transmembrane proteins that are necessary for the normal development of the central nervous system (CNS). While many studies highlight the significance of teneurins, especially during development, there is only limited information known about the molecular mechanisms of function. Previous studies have shown that the N-terminal intracellular domain (ICD) of teneurins can be cleaved at the membrane and subsequently translocates to the nucleus where it can influence gene transcription. Target genes as well as mechanisms have yet to be elucidated, and thus we are investigating the transcriptional activity of the human teneurin-1 ICD in this study. For the whole transcriptome analysis of TEN1-ICD overexpression, we used a modified and improved tet-system. Two separate vectors are required to make the cell line stable. One contains the tet-activating domain fused to a glucocorticoid binding domain (GBD). The other contains the tetO operator sequences directly upstream of a CMV promoter and the gene to be overexpressed. BS149 cells were first transfected with pirtetR-GBD and made stable by Puromycin selection, and then after further transfection with either ptetO-eGFP-His (negative control) or ptetO-TEN1-ICD-eGFP-His by Hygromycin selection. The stable BS149 cell lines were split into three 10 cm Petri dishes each. The triplicate cell lines were cultured once before induction with Dexamethasone and Doxycycline. The overexpressing cells were then FACS-sorted directly into RLT lysis buffer (Qiagen) at a 3:1 volume ratio of lysis buffer to cells in PBS, 24 h post-induction.
2015-02-04 | E-GEOD-61704 | biostudies-arrayexpress
Project description:In this study, we express an activated form of Notch1 in the mouse mammary luminal lineage and analyse the consequences for tumour formation and the transcriptomic landscape in the luminal lineage. Simultaneous conditional activation of a Notch1 intracellular domain (Notch1 ICD) and EGFP in the luminal lineage was achieved by removal of a stop cassette by CRE-recombinase expression from the whey acidic protein (WAP) promoter. Gene expression differences were analysed by single cell RNA-sequencing.
2020-09-20 | GSE137795 | GEO
Project description:Next generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading to constitutive receptor activation were confined to triple negative breast cancers (TNBC, 6 of 66 tumors). TNBC cell lines with NOTCH1 rearrangements associated with high levels of activated NOTCH1 (N1-ICD) were sensitive to the gamma-secretase inhibitor (GSI) MRK-003, both alone and in combination with pacitaxel, in vitro and in vivo, whereas cell lines with NOTCH2 rearrangements were resistant to GSI. Immunohistochemical staining of N1-ICD in TNBC xenografts correlated with responsiveness, and expression levels of the direct Notch target gene HES4 correlated with outcome in TNBC patients. Activating NOTCH1 point mutations were also identified in other solid tumors, including adenoid cystic carcinoma (ACC). Notably, ACC primary tumor xenografts with activating NOTCH1 mutations and high N1-ICD levels were sensitive to GSI, whereas N1-ICD low tumors without NOTCH1 mutations were resistant.
2014-08-14 | GSE59810 | GEO
Project description:Next generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading to constitutive receptor activation were confined to triple negative breast cancers (TNBC, 6 of 66 tumors). TNBC cell lines with NOTCH1 rearrangements associated with high levels of activated NOTCH1 (N1-ICD) were sensitive to the gamma-secretase inhibitor (GSI) MRK-003, both alone and in combination with pacitaxel, in vitro and in vivo, whereas cell lines with NOTCH2 rearrangements were resistant to GSI. Immunohistochemical staining of N1-ICD in TNBC xenografts correlated with responsiveness, and expression levels of the direct Notch target gene HES4 correlated with outcome in TNBC patients. Activating NOTCH1 point mutations were also identified in other solid tumors, including adenoid cystic carcinoma (ACC). Notably, ACC primary tumor xenografts with activating NOTCH1 mutations and high N1-ICD levels were sensitive to GSI, whereas N1-ICD low tumors without NOTCH1 mutations were resistant. Gene expression profiling for Notch-sensitive cancer cell lines using RNA-seq, each sample with triplicates
2014-08-14 | E-GEOD-59810 | biostudies-arrayexpress
Project description:Ogt catalyzed O-linked N-acetylglucosamine (O-GlcNAcylation, O-GlcNAc) plays an important function in diverse biological processes and diseases. However, the roles of Ogt in regulating neurogenesis remain largely unknown. Here, we show that Ogt deficiency or depletion in adult neural stem cells (aNSCs) leads to the diminishment of aNSCs pool and the aberrant neurogenesis, and consequently impairs cognitive function of adult mice. RNA sequencing reveals that Ogt deficiency alters the transcription of genes relating to cell cycle, neurogenesis, and neuronal development. Mechanistic studies show that Ogt directly interacts with Notch1 and catalyzes the O-GlcNAc modification of Notch TM/ICD fragment. The decreased O-GlcNAc modification of TM/ICD increases the binding of E3 ubiquitin ligase Itch to TM/ICD and promotes its degradation. Itch knockdown rescues neurogenic defects in Ogt-deficient mice. OGT also regulates human cortical neurogenesis in forebrain organoids derived from induced pluripotent stem cells. Our findings reveal the essential roles and mechanisms of Ogt and O-GlcNAc modification in regulating mammalian neurogenesis and cognition.
2020-12-15 | GSE163141 | GEO
Project description:We identified histidine triad nucleotide binding protein 1 (HINT1) as a human teneurin-1 ICD interaction partner in a yeast-2 hybrid screen. This interaction was confirmed in human cells, where HINT1 is known to inhibit the transcription of target genes by directly binding to transcription factors at the promoter. In a whole transcriptome analysis of BS149 glioblastoma cells overexpressing the teneurin-1 ICD, several microphthalmia-associated transcription factor (MITF) target genes were found to be up-regulated. Interestingly, MITF is one of the transcription factors inhibited by HINT1. Thus, we directly compare the transcriptomes of MITF versus TEN1-ICD overexpressing BS149 cells in this study, in order to reveal any co-regulated genes.
2015-02-04 | GSE61705 | GEO
Project description:Teneurins are large type II transmembrane proteins that are necessary for the normal development of the central nervous system (CNS). While many studies highlight the significance of teneurins, especially during development, there is only limited information known about the molecular mechanisms of function. Previous studies have shown that the N-terminal intracellular domain (ICD) of teneurins can be cleaved at the membrane and subsequently translocates to the nucleus where it can influence gene transcription. Target genes as well as mechanisms have yet to be elucidated, and thus we are investigating the transcriptional activity of the human teneurin-1 ICD in this study.
2015-02-04 | GSE61704 | GEO
Project description:Irritant contact dermatitis (ICD) is a non-immunological, cutaneous inflammatory response to a variety of triggers that requires no sensitization and accounts for up to 80% of occupational dermatitis cases. Numerous inflammatory cytokines play critical roles in the mechanism and severity of ICD, one being interleukin-6 (IL-6). Therefore, to investigate the influence of this pleotropic cytokine transcriptome analysis (MiSeq) was employed examining irritant-exposed and control skin samples from C57 and IL-6KO mice to gain a better understanding of the immunological mediators of ICD and what role IL-6 plays. Overall, this study offers new insight into the pathogenesis of ICD, indicates new mediators/markers that may influence the variability of responses to irritants and potential targets for therapeutic manipulation.
2018-09-04 | GSE95317 | GEO