We used the CRISPR/Cas9 technique to construct nbr1-KO lines (KO1 and KO3) in order to test the effects of AtNBR1 depletion. Reduced expression of several ABA-up regulated genes were observed in shoots of the two KO lines.
A selective autophagy cargo receptor NBR1 modulates abscisic acid signalling in Arabidopsis thaliana.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.
Sex, Specimen part, Cell line
View SamplesHistone deacetylases (HDACs) have been identified as therapeutic targets due to regulatory function in DNA structure and organization. We have analyzed the role of the LBH589, a novel pan inhibitor of class I and II HDACs, in Acute Lymphoblastic Leukemia. In vitro, LBH589 was shown to induce a dose dependent antiproliferative and apoptotic effect which was associated with an increase in the acetylation of H3 and H4 histone acetylation which was uniformly in every genetic subgroup of ALL. In vivo administration of LBH589 in BALB/c-RAG2-/-c-/- mice in which T and B-cell leukemic cell lines were injected induced a significant reduction in tumor growth (TOM-1, p<0.01 and MOLT-4 p<0.05). Leukemic cells from patients were employed to establish a xenograft model of human leukemia in BALB/c-RAG2-/-c-/- mice and further transplanted in consecutive generations of mice. Treatment of these xenografts with LBH589 induced an increase in the acetylation of H3 and H4 and prolonged the survival of mice in comparison with the animals treated with Vincristine and Dexametasone (p<0.05) and this effect was significantly higher when LBH589 was combined with Vincristine and Dexametasone (p<0.001). Our results that the use of LBH589 in combination with standard chemotherapy represents an attractive option for treatment of patients with ALL.
Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Specificity and heterogeneity of terahertz radiation effect on gene expression in mouse mesenchymal stem cells.
Specimen part
View SamplesThe Myc proteins (N-, L- and c-Myc) are transcription factors involved in many biological functions such as regulation of cell proliferation, differentiation, metabolism and apoptosis. A large number of human cancers show enhanced expression of myc family proto-oncogenes as one of their hallmarks. These proteins contain a basic region/helix-loop-helix/leucine zipper (bHLHZip) domain that mediates DNA binding and heterodimerization with its partner Max (Myc/Max heterodimer). Among Myc proteins, c-Myc is the most widely expressed and relevant in primary B lymphocytes. Some reports have implied that c-Myc can perform some functions without Max in different cell contexts. However, the functional interplay in vivo between c-Myc and Max during B lymphocyte differentiation is not well-known. Here we show that c-Myc requires Max. However, key biological processes such as cell differentiation and DNA replication can initially progress without c-Myc/Max heterodimer in primary B lymphocytes. We found that B lymphocytes lacking Myc, Max or both showed upregulation of signalling pathways associated with the B cell receptor. Our data suggest that c-Myc/Max heterodimers are not essential for the initiation of certain biological processes in B lymphocytes. Rather, c-Myc/Max are necessary for fine-tuning the initial response in these cells after activation. Overall design: B cell mRNA profiles of 8-week old control (HET) Myc deficient (MycKO), Max deficient (MaxKO) and double deficient (DKO) mice were generated by deep sequencing, in duplicate, using a HiSeq2500 (Illumina.
Functional interplay between c-Myc and Max in B lymphocyte differentiation.
Age, Specimen part, Subject
View SamplesWe report that terahertz (THz) irradiation of mouse mesenchymal stem cells with a pulsed broadband (centered at 10 THz) source, or a single-frequency, 2.52 THz, (SF) laser source, both with weak average power (<1mW/cm2), results in specific heterogenic changes in gene expression. The insignificant differential expression of heat shock and stress related genes as well as our temperature measurements imply a non-thermal response. The microarray survey and RT-PCR experiments demonstrate that at different irradiation conditions distinct groups of genes are activated. Stem cells irradiated for 12 hours with the broadband THz source exhibit an accelerated differentiation toward adipose phenotype, while the 2-hour (broadband or SF) irradiation affects genes transcriptionally active in pluripotent stem cells. Phenotypic and gene expression differences suggest that the THz effect depends on irradiation parameters such as duration and type of THz source, and on the level of stem cell differentiation. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression.
Specificity and heterogeneity of terahertz radiation effect on gene expression in mouse mesenchymal stem cells.
Specimen part
View SamplesWe report that terahertz (THz) irradiation of mouse mesenchymal stem cells with a pulsed broadband (centered at 10 THz) source, or a single-frequency, 2.52 THz, (SF) laser source, both with weak average power (<1mW/cm2), results in specific heterogenic changes in gene expression. The insignificant differential expression of heat shock and stress related genes as well as our temperature measurements imply a non-thermal response. The microarray survey and RT-PCR experiments demonstrate that at different irradiation conditions distinct groups of genes are activated. Stem cells irradiated for 12 hours with the broadband THz source exhibit an accelerated differentiation toward adipose phenotype, while the 2-hour (broadband or SF) irradiation affects genes transcriptionally active in pluripotent stem cells. Phenotypic and gene expression differences suggest that the THz effect depends on irradiation parameters such as duration and type of THz source, and on the level of stem cell differentiation. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression.
Specificity and heterogeneity of terahertz radiation effect on gene expression in mouse mesenchymal stem cells.
Specimen part
View SamplesWe report that terahertz (THz) irradiation of mouse mesenchymal stem cells with a pulsed broadband (centered at 10 THz) source, or a single-frequency, 2.52 THz, (SF) laser source, both with weak average power (<1mW/cm2), results in specific heterogenic changes in gene expression. The insignificant differential expression of heat shock and stress related genes as well as our temperature measurements imply a non-thermal response. The microarray survey and RT-PCR experiments demonstrate that at different irradiation conditions distinct groups of genes are activated. Stem cells irradiated for 12 hours with the broadband THz source exhibit an accelerated differentiation toward adipose phenotype, while the 2-hour (broadband or SF) irradiation affects genes transcriptionally active in pluripotent stem cells. Phenotypic and gene expression differences suggest that the THz effect depends on irradiation parameters such as duration and type of THz source, and on the level of stem cell differentiation. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression.
Specificity and heterogeneity of terahertz radiation effect on gene expression in mouse mesenchymal stem cells.
Specimen part
View SamplesWe report that extended exposure to broad-spectrum terahertz radiation results in specific changes in cellular functions that are closely related to DNA-directed gene transcription. Our gene chip survey of gene expression shows that whereas 89% of the protein coding genes in mouse stem cells do not respond to the applied teraherz radiation, certain genes are activated, while other are repressed. RT-PCR experiments with selected gene probes corresponding to transcripts in the three groups of genes detail the gene specific effect. The response was not only gene specific but also irradiation conditions dependent. Our findings suggest that the applied terahertz irradiation accelerates cell differentiation toward adipose phenotype by activating the transcription factor peroxisome proliferator-activated receptor gamma (PPARG). Finally, our molecular dynamics computer simulations indicate that the local breathing dynamics of the PPARG promoter DNA coincides with the gene specific response to the THz radiation. We propose that THz radiation is a potential tool for cellular reprogramming.
Mammalian stem cells reprogramming in response to terahertz radiation.
Specimen part, Treatment
View SamplesDouble Hit Lymphoma (DHL) were treated with the BRD4 inhibitor 100 nM CPI203 for 6h
The BET bromodomain inhibitor CPI203 overcomes resistance to ABT-199 (venetoclax) by downregulation of BFL-1/A1 in in vitro and in vivo models of MYC+/BCL2+ double hit lymphoma.
Specimen part, Cell line, Subject
View Samples