Pre-B and pre-T lymphocytes must orchestrate a transition from a highly proliferative state to a quiescent one during development. Cyclin D3 is essential for these cells’ proliferation, but little is known about its post-translational regulation at this stage. Here, we show that the dual specificity tyrosine-regulated kinase 1A (DYRK1A) restrains Cyclin D3 protein levels by phosphorylating T283 to induce its degradation. Loss of DYRK1A activity, via genetic inactivation or pharmacologic inhibition, caused accumulation of Cyclin D3 protein, incomplete repression of E2F-mediated gene transcription, and failure to properly couple cell cycle exit with differentiation. Expression of a non-phosphorylatable Cyclin D3 T283A mutant recapitulated these defects, while inhibition of Cyclin D:CDK4/6 mitigated the effects of DYRK1A inhibition. These data uncover a previously unknown role for DYRK1A in lymphopoiesis, and demonstrate how Cyclin D3 protein stability is negatively regulated during exit from the proliferative phases of B and T cell development. Overall design: 5 cell populations were analyzed (small pre-B cells, large pre-B cells, quiescent CD4+CD8+ thymocytes, cycling CD4+CD+ thymocytes, and mature granulocytes) from 2 Control mice (pooled) and 2 DYRK1A-deficient mice (pooled) for a total of 10 samples.
DYRK1A controls the transition from proliferation to quiescence during lymphoid development by destabilizing Cyclin D3.
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View SamplesAnalysis of the gene expression level of 4T1 orthotopic tumors in mice with and without pericyte depletion.
Targeting vascular pericytes in hypoxic tumors increases lung metastasis via angiopoietin-2.
Specimen part, Treatment
View SamplesGenetically engineered mice developed spontaneous pancreas cancer (Pdx-Cre;LSL-KRASG12D;P53Mut). Mice were also engineered to develop similar spontaneous pancreas cancer without Twist or Snail (conditional gene knockout). The pancreas tumors were harvested and analysed for gene expression profiles comparisons.
Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer.
Specimen part
View SamplesRegulatory T (Treg) cells play an indispensable role in immune homeostasis. The development and function of Tregs are dependent on transcriptional factor Foxp3, but how constant expression of Foxp3 is maintained in Tregs is not clear. Here we show that ablation of the conserved non-coding DNA sequence 2 (CNS2) at the Foxp3 locus in mice led to spontaneous lymphoproliferative disease and exacerbation of experimental autoimmune encephalomyelitis (EAE). CNS2 is required for activated Treg cells to maintain elevated Foxp3 expression, which is critical for their suppressor function and lineage stability. Mechanistically, upon TCR stimulation, NFAT binds to both CNS2 and Foxp3 promoter and mediates the interaction between CNS2 and Foxp3 promoter. Our findings demonstrated an essential role for CNS2 in maintaining the stability and function of activated Treg cells and identified NFAT as a key mediator of its function. Overall design: Gene expression was profiled in T regulatory cells (Treg) in WT and CNS2 knockout mice. CNS2 knockout mice lack a conserved non-coding DNA sequence 2 (CNS2) at the Foxp3 locus. Treg cells were further sorted into Foxp3-high and Foxp3-low populations based on the expression level of Foxp3. mRNA was profiled using RNA-Seq (unstranded, polyA+, SE100) in replicate for each condition
Function of a Foxp3 cis-element in protecting regulatory T cell identity.
No sample metadata fields
View SamplesIn this study Panc-1 cells and BxPC-3 cells were cultured. The cells were harvested (untreated control 'cont') for RNA extraction, or treated for 3 hours with various exosomes preparations. The exosomes were collected from BJ human foreskin fibroblast culture supernatant without further processing (control exosomes or 'CE'), or engineered to contain scrambled siRNA ('scr') or KRASG12D siRNA ('iExo). Two or three distinct wells of cells were evaluated per treatment condition and assigned a well number (well -1, -2 or 3).
Generation and testing of clinical-grade exosomes for pancreatic cancer.
Cell line, Treatment
View Samplesaffy_pop_2011_08 - poplar bent study - genes regulated by PtaZFP2 in absence of mechanical stress - genes regulated by PtaZFP2 after one bending.Species: Populus tremula x Populus alba-- The laboratory previously established a poplar transgenic line overexpressing PtaZFP2 under the control of an estradiol-inducible promoter. - the experiment, conducted on 3-month-old hydroponically-grown poplars, consists in the comparison of WT poplars treated with estradiol and the PtaZFP2-overexpressing line treated with estradiol. We also compared unbent and bent PtaZFP2-overexpressing poplars. The applied strain is quantitatively controlled (Coutand & Moulia, 2000, JExpBot; coutand et al., 2009, Plant Physiology) -
The zinc finger protein PtaZFP2 negatively controls stem growth and gene expression responsiveness to external mechanical loads in poplar.
Treatment
View SamplesBackground: Epithelial-to-Mesenchymal Transition (EMT) is predicted to play a critical role in tumor progression and metastasis in Hepatocellular Carcinoma. Our goal was to elucidate a mechanism of tumor proliferation and metastasis using a novel murine model of EMT.
Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion.
Specimen part
View SamplesGiven that the NF-B pathway plays an important role in tumor development and that IKK2 is the seminal kinase responsible for NF-B pathway activation, we were particularly interested in exploring the therapeutic potential of IKK2 inhibition in non-small cell lung cancers.
Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model.
Specimen part
View Samplesaffy_pop_2011_08 - poplar estradiol study - genes regulated by PtaZFP2 in absence of mechanical stress - genes regulated by PtaZFP2 after one bending.Species: Populus tremula x Populus alba-The laboratory previously established a poplar transgenic line overexpressing PtaZFP2 under the control of an estradiol-inducible promoter. - the experiment, conducted on 3-month-old hydroponically-grown poplars, consists in the comparison of WT poplars treated with estradiol and the PtaZFP2-overexpressing line treated with estradiol. We also compared unbent and bent PtaZFP2-overexpressing poplars. The applied strain is quantitatively controlled (Coutand & Moulia, 2000, JExpBot; coutand et al., 2009, Plant Physiology)
The zinc finger protein PtaZFP2 negatively controls stem growth and gene expression responsiveness to external mechanical loads in poplar.
Treatment
View SamplesLPA is a natural bioactive lipid with growth factor-like functions due to activation of series of six G protein-coupled receptors (LPA1-6).
Identification of heparin-binding EGF-like growth factor (HB-EGF) as a biomarker for lysophosphatidic acid receptor type 1 (LPA1) activation in human breast and prostate cancers.
Cell line
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