E-MTAB-6898
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ABSTRACT:
PROVIDER: E-MTAB-6898 | ExpressionAtlas | 2023-06-15
REPOSITORIES: ExpressionAtlas
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Project description:Since loss of Hes1 and Notch signalling drives progenitors to the endocrine lineage, we set up a pancreas explant system with crosses of heterozygous Neurog3tTA/+, a knock-in allele which makes the homozygote Neurog3tTA/tTA embryos deficient in Neurog3 (hereafter Neurog3-null). Hereby endocrine differentiation is impeded and we can study the Neurog3-independent role of Notch signalling by DAPT inhibition of γ-secretase. E12.5 wildtype and Neurog3-null pancreata were explanted on fibronectin, grown for 3 days, and then treated with vehicle control (0.1% DMSO) or DAPT for 24h. RNA was isolated and subjected to Agilent microarray analysis
2022-02-27 | E-MTAB-6898 | biostudies-arrayexpress
Project description:gene expression profiles in fly brains between wildtype and miR-34 null flies gene expression profiles in fly brains, wild type (3d, 20d) and miR-34 null flies (3d, 20d)
2011-12-23 | E-GEOD-25008 | biostudies-arrayexpress
Project description:Omental adipose tissue explants were cultured for 24h in serum-free medium in the presence of vehicle (control medium) or macrophage (LPS) and T-cell (anti-CD3/28) stimulants (active medium). SGBS human preadipocytes were differentiated into adipocytes and then exposed to 25% v/v control or active medium.
2016-12-01 | GSE75710 | GEO
Project description:In leukemogenesis Notch signaling can be up- and down-regulated in a context-dependent manner. Here we report that deletion of hairy and enhancer of split-1 (Hes1) promotes acute myeloid leukemia (AML) development induced by the MLL-AF9 fusion protein. Subsequently, the FMS-like tyrosine kinase 3 (FLT3) was up-regulated in mouse cells of a Hes1- or RBP-J-null background. MLL-AF9-expressing Hes1-null AML cells showed enhanced proliferation and ERK phosphorylation following FLT3 ligand stimulation. FLT3 inhibition efficiently abrogated proliferation of MLL-AF9-induced Hes1-null AML cells. Furthermore, an agonistic anti-Notch2 antibody induced apoptosis of MLL-AF9-induced AML cells in a Hes1-wild type but not a Hes1-null background. These observations demonstrate that Hes1 mediates tumor suppressive roles of Notch signaling in AML development by down-regulating FLT3 expression.
2017-05-02 | GSE50234 | GEO
Project description:In leukemogenesis Notch signaling can be up- and down-regulated in a context-dependent manner. Here we report that deletion of hairy and enhancer of split-1 (Hes1) promotes acute myeloid leukemia (AML) development induced by the MLL-AF9 fusion protein. Subsequently, the FMS-like tyrosine kinase 3 (FLT3) was up-regulated in mouse cells of a Hes1- or RBP-J-null background. MLL-AF9-expressing Hes1-null AML cells showed enhanced proliferation and ERK phosphorylation following FLT3 ligand stimulation. FLT3 inhibition efficiently abrogated proliferation of MLL-AF9-induced Hes1-null AML cells. Furthermore, an agonistic anti-Notch2 antibody induced apoptosis of MLL-AF9-induced AML cells in a Hes1-wild type but not a Hes1-null background. These observations demonstrate that Hes1 mediates tumor suppressive roles of Notch signaling in AML development by down-regulating FLT3 expression. 4 samples are analyzed, two pairs of MLL-AF9/Hes1-/- and MLL-AF9/Hes1+/+ leukemic bone marrows.
2017-05-02 | E-GEOD-50234 | biostudies-arrayexpress
Project description:Identification of factors in conditioned media of first-trimester placental villous explants. Explants were cultured under hypoxia (2% O2), 5% CO2 in serum-free DMEM/F12 and treated with recombinant galectin-7 (1ug/ml) or vehicle control (BSA) for 72h. Identification of factors in conditioned media of first-trimester placental villous explants. Explants were cultured under superoxia (20% O2), 5% CO2 in serum-free DMEM/F12 and treated with recombinant galectin-7 (1ug/ml) or vehicle control (BSA) for 72h.
2021-04-20 | PXD019331 | Pride
Project description:We performed single-cell RNA-sequencing of 3D endometrial organoid cultures in order to dissect the signaling pathways that determine cell fate of epithelial lineages. Every time course was obtained in a background that either included or did not include ovarian hormones stimulation, which emulates dynamic regulations associated with the menstrual cycle. These inductions show that in vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively.
2021-07-21 | E-MTAB-10283 | biostudies-arrayexpress
Project description:Analysis of epithelial explants injected with the intracellular domain of Notch (ICD) to block the formation of multi-ciliate and proton secreting cells or with dominant negative human Mastermind (HMM) or a DNA binding mutant of Mastermind (DBM) to induce the formation of ectopic multi-ciliate and proton secreting cells. Results show which genes are up or down-regulated when DBM/HMM are compared to ICD. Epithelial cells projecting hundreds of motile cilia are prominent in the respiratory system, brain ependyma and female reproductive tract where they generate a vigorous fluid flow along luminal surfaces. Despite their importance for organ function, how multiciliate cells arise developmentally in diverse epithelia is poorly understood. Notch signaling has been shown in a variety of tissues, including the Xenopus epithelium, to regulate the formation of multiciliate cell precursors. In order to identify early downstream targets of Notch signaling which contribute to multiciliate cell fate we blocked or activated Notch signaling in explants of Xenopus epithelium and looked at changes in gene expression to identify candidates that regulate multiciliate cell fate. Here we identify a novel coiled-coil protein, called multicilin (MCI), whose expression is Notch-regulated and restricted to epithelia where multiciliate cells forms in Xenopus embryos. Inhibiting MCI activity blocks the formation of multiciliate cell precursors while ectopic MCI activity is sufficient to induce multiciliate cell differentiation within epithelial progenitors. 2-cell stage Xenopus embryos were injected with synthetic mRNA encoding ICD, DBM or HMM. At stage 9/10 the presumptive ectoderm was cut off the embryo and cultured on a fibronectin coated coverslip. At stage 12 RNA was harvested from explants and used as the starting material for arrays.
2012-03-01 | E-GEOD-32331 | biostudies-arrayexpress
Project description:Notch signaling is frequently hyperactivated in breast cancer, but how the enhanced signaling contributes to the tumor process is less well understood. In this report, we identify the proinflammatory cytokine interleukin-6 (IL-6) as a novel Notch target in breast tumor cells. Enhanced Notch signaling upregulated IL-6 expression at the transcriptional level, leading to activation of autocrine and paracrine JAK/STAT signaling. IL-6 upregulation was mediated by non-canonical Notch signaling, as it could be effectuated by a cytoplasmically localized Notch intracellular domain and was independent on the DNA-binding protein CSL. Instead, Notch-mediated IL-6 upregulation was controlled by two other factors: IKKβ, a protein in the NF-kB signaling cascade, and p53. Activation of IL-6 by Notch required IKKβ function, but interestingly, did not engage canonical NF-κB signaling, in contrast to IL-6 activation by inflammatory agents such as tumor necrosis factor, which requires canonical NF-κB signaling. With regard to p53 status, IL-6 expression was upregulated by Notch when p53 was mutated or lost, but restoring wildtype 53 into p53-mutated or -deficient cells abrogated the IL-6 upregulation. Furthermore, Notch-induced genome-wide transcriptomes from p53 wildtype and -mutated breast tumor cell lines differed extensively, and in a subset of genes upregulated by Notch in a p53-mutant cell line, upregulation was reduced by wildtype p53. In conclusion, we identify IL-6 as a novel non-canonical Notch target gene, and reveal roles for p53 and IKKβ in non-canonical Notch signaling in breast cancer and in the generation of cell context-dependent diversity in the Notch signaling output.
2012-06-30 | GSE36051 | GEO
Project description:RNA-seq of FACS Sorted E10.5 Pdx1-GFP+ of genotypes wildtype and Hes1-/-. Summary statement The developmental mechanisms that cause ectopic pancreas are poorly understood. We show that aberrant dorsal pancreas morphogenesis in Hes1 mutants leads to ectopic pancreas depending on the pro-endocrine gene Neurog3. Abstract Mutations in Hes1, a target gene of the Notch signalling pathway, lead to ectopic pancreas by a poorly described mechanism. Here we use genetic inactivation of Hes1 combined with lineage tracing in mouse embryos to reveal an endodermal requirement for Hes1 and that most ectopic pancreas tissue is derived from the E8.5 dorsal pancreas primordium. RNA-seq data from sorted E10.5 Pdx1-GFP+ cells from Hes1+/+ and Hes1−/− suggested that upregulation of endocrine lineage genes in Hes1−/− embryos was the major defect in the endoderm and accordingly early pancreas morphogenesis was normalised and the ectopic pancreas phenotype suppressed in Hes1−/−Neurog3−/− embryos. Analysis of other Notch pathway mutants uncovered a total depletion of progenitors in Mib1 deficient dorsal anlage, which was replaced by an anterior Gcg+ extension. Together, our results demonstrate that aberrant morphogenesis is the cause of ectopic pancreas and that a part of the endocrine differentiation program is mechanistically involved in the dysgenesis. Our results suggest that the ratio of endocrine lineage to progenitor cells is important for morphogenesis and that a strong endocrinogenic phenotype without complete progenitor depletion as seen in Hes1 mutants provokes an extreme dysgenesis that causes ectopic pancreas.
2018-08-20 | E-MTAB-6890 | biostudies-arrayexpress