Expression data from embryonic stem cells following siRNA transfection of UPS members
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Shannon Buckley
PROVIDER: E-GEOD-39772 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:While transcriptional regulation of stem cell self-renewal and differentiation has been extensively studied, only a small number of studies have addressed the roles for post-translational modifications in these processes. A key mechanism of post-translational modification is ubiquitination by the ubiquitin-proteasome system (UPS). Using UPS-targeted RNAi screens, we identify novel regulators of pluripotency and differentiation. We focus on two of these proteins, the deubiquitinating enzyme, Psmd14, and the E3 ligase, Fbxw7, and characterize their importance in ES cell pluripotency and cellular reprogramming. Embryonic stem cells were reverse transfected with siRNA, 48 hrs post transfection cells were isloated for RNA extraction and hybridization on Affymetrix microarrays
2012-07-31 | E-GEOD-39771 | biostudies-arrayexpress
Project description:While transcriptional regulation of stem cell self-renewal and differentiation has been extensively studied, only a small number of studies have addressed the roles for post-translational modifications in these processes. A key mechanism of post-translational modification is ubiquitination by the ubiquitin-proteasome system (UPS). Using UPS-targeted RNAi screens, we identify novel regulators of pluripotency and differentiation. We focus on two of these proteins, the deubiquitinating enzyme, Psmd14, and the E3 ligase, Fbxw7, and characterize their importance in ES cell pluripotency and cellular reprogramming. Embryonic stem cells were reverse transfected with siRNA, and differentiated for 48hrs in conditions with retinoic acid, 48 hrs post transfection cells were isloated for RNA extraction and hybridization on Affymetrix microarrays
2012-07-31 | E-GEOD-39770 | biostudies-arrayexpress
Project description:Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2). E13.5 Foetal Liver lineage negative, cKit+, Sca1+ cells were sorted from Hes-GFP mice for RNA extraction and hybridization on Affymetrix microarrays
2013-07-01 | E-GEOD-46725 | biostudies-arrayexpress
Project description:Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2). Bone marrow lineage negative, cKit+, Sca1- cells were sorted from Hes-GFP mice for RNA extraction and hybridization on Affymetrix microarrays
2013-07-01 | E-GEOD-46723 | biostudies-arrayexpress
Project description:Notch signaling defines a conserved, fundamental pathway, responsible for determination in metazoan development and is widely recognized as an essential component of lineage specific differentiation and stem cell self-renewal in many tissues including the hematopoietic system. Until recently, the majority of studies in the hematopoietic system focused on Notch signaling in lymphocyte differentiation and knowledge of individual Notch receptor roles in early hematopoiesis has been limited due to a paucity of genetic tools available To fate-map Notch receptor expression and pathway activity in the hematopoietic system we used tamoxifen-inducible CreER knock-in mice for individual Notch receptors in combination to a novel Notch reporter strain (Hes1GFP) and a conditional gain of function allele of Notch2 receptor (Rosa-lsl-ICN2). Bone marrow lineage negative, cKit+, Sca1+ cells were sorted from Hes-GFP mice for RNA extraction and hybridization on Affymetrix microarrays
2013-07-01 | E-GEOD-46722 | biostudies-arrayexpress
Project description:Missense FBXW7 mutations are prevalent in various tumors, including T-cell acute lymphoblastic leukemia (T-ALL). To study the effects of such lesions, we generated animals carrying regulatable Fbxw7 mutant alleles. We show here that these mutations specifically bolster cancer-initiating cell activity in collaboration with Notch1 oncogenes, but spare normal hematopoietic stem cell function. We were also able to show that FBXW7 mutations specifically affect the ubiquitylation and half-life of c-Myc protein, a key T-ALL oncogene. Using animals carrying c-Myc fusion alleles, we connected Fbxw7 function to c-Myc abundance and correlated c-Myc expression to leukemia-initiating activity. Three independent Notch1 T-ALL were derived on c-Myc-GFP background and sorted from the spleen of leukemic mice on the basis of GFP expression for RNA extraction and hybridization on Affymetrix microarrays
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Project description:Cyclin D3 is critical hematopoiesis and loss of cyclin D3 leads to resistance to transformation of bone marrow progenitors by Notch1-IC. We used a small molecule targeting cyclin D3:CDK4/6 activity to study whether its inhibition is an effective therapeutic strategy. We analyzed T-ALL lines in vitro with PD-0332991 or vehicle control to determine genes affected by the drug. CEM, Jurkat, DND41, and CUTL-1 cell lines were treated with 1 uM PD-0332991 or DMSO for 15 hours prior to RNA extraction and hybridization to Human Genome U133 Plus 2.0 Affymetrix arrays.
2012-12-13 | E-GEOD-40635 | biostudies-arrayexpress
Project description:Recurrent somatic mutations in TET2 and in other genes that regulate the epigenetic state have been identified in patients with myeloid malignancies and in other cancers. However, the in vivo effects of Tet2 loss have not been delineated. We report here that Tet2 loss leads to increased stem-cell self-renewal and to progressive stem cell expansion. Consistent with human mutational data, Tet2 loss leads to myeloproliferation in vivo, notable for splenomegaly and monocytic proliferation. In addition, haploinsufficiency for Tet2 confers increased self-renewal and myeloproliferation, suggesting that the monoallelic TET2 mutations found in most TET2-mutant leukemia patients contribute to myeloid transformation. This work demonstrates that absent or reduced Tet2 function leads to enhanced stem cell function in vivo and to myeloid transformation. These studies show that a ubiquitin ligase-substrate pair can orchestrate the molecular program of HSC differentitiation Gene expression profiles from WT and Tet2-/- sorted LSK and myeloid progenitors (CMP and GMP) were compared using genome wide mRNA expression profiling by Affymetrix genechip arrays (Mouse 430 2.0) and key targets were validated by chromatin immunoprecipitation experiments.
2011-07-01 | E-GEOD-27816 | biostudies-arrayexpress
Project description:Notch signaling is one of the central regulators of differentiation in a variety of organisms and tissue types. Within the hematopoietic system, Notch is essential for the emergence of definitive HSC during fetal life and controls adult HSC differentiation to the T-cell lineage. Notch activation is controlled by the gamma-secretase complex complex, composed of presenilin, nicastrin (Ncstn), anterior pharynx-1 (Aph1), and presenilin enhancer-2 To determine other role of Notch signaling in HSC we designed a conditional mouse model of Nicastrin deletion. WT and KO HSC were analysed to determined genes controlled by Notch signaling. Bone marrow lineage negative, cKit+, Sca1+ and lineage negative, cKit+, Sca1- CD34+ FcgammaRII/III+ cells were sorted from WT and Ncstn KO littermates for RNA extraction and hybridization on Affymetrix microarrays
2011-05-12 | E-GEOD-27811 | biostudies-arrayexpress
Project description:Expression data from untreated or Dll4-Fc treated THP1 cell line. We used Dll4-Fc stimulation of AML cells to study whether Notch activation has an impact on AML. We analyzed THP1 cell line in vitro treated with Dll4-Fc or vehicle control to determine genes affected by Notch activation. THP1 cell line was cultured on plate coated with 30 nM Dll4-Fc or vehicle for 48 hours prior to RNA extraction and hybridization to Human Genome U133 Plus 2.0 Affymetrix arrays.
2013-01-18 | E-GEOD-42259 | biostudies-arrayexpress