Rice transgenic plants of the bZIP encoding gene, OsbZIP48, in the Pusa Basmati 1 (PB1) variety have been found to display differences in the total height. In order to elucidate changes at the transcriptome level, microarray of the 10-day-old seedlings of over-expresseion (OE) and knock-down (KD) lines along with vector control (VC) were carried out.
OsbZIP48, a HY5 Transcription Factor Ortholog, Exerts Pleiotropic Effects in Light-Regulated Development.
Age, Specimen part
View SamplesFresh Atypical ductal hyperplasia (ADH) tissue collected from breast of a women who either (1) had no prior history of breast cancer and had not developed breast cancer in five years after diagnosis, (2) had cancer before ADH, or had cancer at the time as ADH or developed cancer after ADH diagnosis
Identification of MMP-1 as a putative breast cancer predictive marker by global gene expression analysis.
No sample metadata fields
View SamplesThis study investigates three radiation exposure scenarios in BALB/c and C57BL/6 mice: (1) low dose (LD) group -- four weekly doses of 7.5 cGy, (2) high dose (HD) group -- four weekly doses of 1.8 Gy, (3) unexposed group -- four weekly sham exposures. We then used comparative expression profiles of the mouse mammary gland and cardiac blood to build a model of candidate tissue functions associated with LD cancer susceptibility in these strains and murine and human knowledgebases to characterize these tissue functions and their relevance to breast cancer.
Genetic differences in transcript responses to low-dose ionizing radiation identify tissue functions associated with breast cancer susceptibility.
Sex, Age, Specimen part
View SamplesThe crizotinibresistant ALKF1174L mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel ALK inhibitors with different modes of action. The diaminopyrimidine TAE684 and its derivative ceritinib (LDK378), which are structurally distinct from crizotinib, are active against NB cells expressing ALKF1174L. Here we demonstrate acquired resistance to TAE684 and LDK378 in ALKF1174L-driven human NB cells that is linked to overexpression and activation of the AXL tyrosine kinase and epithelial-to-mesenchymal transition (EMT). AXL phosphorylation conferred TAE684 resistance to NB cells through upregulated ERK signaling. Inhibition of AXL partly rescued TAE684 resistance, resensitizing these cells to this compound. AXL activation in resistant cells was mediated through increased expression of the active form of its ligand, GAS6, which also served to stabilize the AXL protein. Although ectopic expression of AXL and TWIST2 individually in TAE684-sensitive parental cells led to the elevated expression of mesenchymal markers and invasive capacity, only AXL overexpression induced resistance to TAE684 as well. TAE684-resistant cells showed greater sensitivity to HSP90 inhibition than did their parental counterparts, with downregulation of AXL and AXL-mediated ERK signaling. Our studies indicate that aberrant AXL signaling and development of an EMT phenotype underlie resistance of ALKF1174L-driven NB cells to TAE684 and its derivatives. We suggest that the combination of ALK and AXL or HSP90 inhibitors be considered to delay the emergence of such resistance.
ALK inhibitor resistance in ALK(F1174L)-driven neuroblastoma is associated with AXL activation and induction of EMT.
Specimen part, Cell line
View SamplesDysregulated inflammation is implicated in the pathobiology of aging, yet platelet-leukocyte interactions and downstream inflammatory gene synthesis in older adults remains poorly understood. Highly-purified human platelets and monocytes were isolated from healthy younger (age<45, n=37) and older (age60, n=30) adults and incubated together under autologous and non-autologous conditions. Inflammatory gene synthesis by monocytes, basally and in the presence of platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in aging. Basal IL-8 and MCP-1 synthesis by monocytes alone did not differ between older and younger adults. However, in the presence of autologous platelets, monocytes from older adults synthesized greater IL-8 (415 vs. 92 ng/mL, p<0.0001) and MCP-1 (867150 vs. 21636 ng/mL, p<0.0001) than younger adults. Non-autologous experiments demonstrated that platelets from older adults were sufficient for upregulating inflammatory gene synthesis by monocytes. Using RNA-seq followed by validation via RT-PCR and immunoblot, we discovered that granzyme A (GrmA), a serine protease not previously identified in human platelets, is increased in aging (~9-fold vs. younger adults, p<0.05) and governs increased IL-8 and MCP-1 synthesis through TLR4 and caspase-1. Inhibiting GrmA reduced the excessive IL-8 and MCP-1 synthesis in older adults to levels similar to younger adults. In summary, human aging is associated with changes in the platelet transcriptome and proteome. GrmA is present and bioactive in human platelets, is higher in older adults, and controls inflammatory gene synthesis by monocytes. Alterations in the platelet molecular signature and downstream signaling to monocytes may contribute to dysregulated inflammatory syndromes and adverse outcomes in older adults.
Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory Cytokines by Monocytes in Aging.
Sex, Age, Specimen part, Disease
View SamplesThe heart uses primarily fatty acids and glucose for deriving energy. The majority of energy in the healthy heart derives from fat utilization, with the remainder coming primarily from the catabolism of glucose. Classical studies by Randle and colleagues describe the ability of the heart to switch its mode of utilization facilely and reversibly between glucose and fatty acids (myocardial glucose-fatty acid cycle or Randle cycle). However, under conditions of pathological stress, reliance of the heart on fatty acids decreases with a concomitant increase in reliance on glucose. It is unclear how such changes in metabolism regulate gene expression in the heart. Therefore, we examined how regulation of glycolysis at the level of phosphofructokinase modulates gene expression in the heart. We performed transcriptomic analysis of hearts from mice expressing either kinase-deficient phosphofructokinase 2 (GlycoLo) or phosphatase-deficient phosphofructokinase 2 (GlycoHi) under the control of the -MHC promoter, which restricted expression of the transgenes to the heart. Phosphofructokinase 2 only controls the ability of the myocyte to regulate abundance of a single metabolite, F-2,6-P2, which is an allosteric regulator of the rate-limiting and committed step in glycolysis. Parallel radiometric and metabolomic studies showed the expected increases or decreases in glycolytic flux along with diametrically opposite changes in fat metabolism, which is consistent with the myocardial glucose-fatty acid cycle. Transcriptomic analyses showed remarkable changes in gene transcription in these hearts, which indicates that glucose and/or fatty acid metabolism is a driver of transcriptional programs in the heart. Furthermore, glycolytic activity coordinately regulated numerous genes in the heart, including genes important for cardiac remodeling as well as genes regulating gluconeogenic and ancillary biosynthetic pathway activity. These findings reveal that glycolytic rate is a critical regulator of gene expression in the heart and can coordinate programs that modulate cardiac metabolism, growth, and hypertrophy.
Exercise-Induced Changes in Glucose Metabolism Promote Physiological Cardiac Growth.
Sex, Age, Specimen part
View SamplesWe report the gene expression comparison of zebrafish melanocytes and melanomas. These comparisons were used for integrative genomic studies that identified the BMP factor GDF6 as a new oncogene that is specifically expressed in melanomas. Overall design: Examination of gene expression in two different cell types
Ligand-activated BMP signaling inhibits cell differentiation and death to promote melanoma.
No sample metadata fields
View SamplesTherapy-related myelodysplasia or acute myeloid leukemia (t-MDS/AML) is a lethal complication of cancer treatment. Although t-MDS/AML development is associated with known genotoxic exposures, its pathogenesis is not well understood and methods to predict risk of development of t-MDS/AML in individual cancer survivors are not available. We performed microarray analysis of gene expression in samples from patients who developed t-MDS/AML after autologous hematopoietic cell transplantation (aHCT) for Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) and controls that did not develop t-MDS/AML after aHCT. CD34+ progenitor cells from peripheral blood stem cell (PBSC) samples obtained pre-aHCT from t-MDS/AML cases and matched controls, and bone marrow (BM) samples obtained at time of development of t-MDS/AML, were studied. Significant differences in gene expression were seen in PBSC obtained pre-aHCT from patients who subsequently developed t-MDS/AML compared to controls. Genetic alterations in pre-aHCT samples were related to mitochondrial function, protein synthesis, metabolic regulation and hematopoietic regulation. Progression to overt t-MDS/AML was associated with additional alterations in DNA repair and DNA-damage checkpoint genes. Altered gene expression in PBSC samples were validated in an independent group of patients. An optimal 63-gene PBSC classifier derived from the training set accurately distinguished patients who did or did not develop t-MDS/AML in the independent test set. These results indicate that genetic programs associated with t-MDS/AML are perturbed long before disease onset, and can accurately identify those at risk of developing this complication.
Altered hematopoietic cell gene expression precedes development of therapy-related myelodysplasia/acute myeloid leukemia and identifies patients at risk.
Disease, Subject
View SamplesGjd3-CreEGFP mice is a novel genetic tool to study the structural and molecular signatures of Atrioventricular Node (AVN) at a high resolution. Overall design: Focusing on the cardiac conduction system, we developed and rigorously characterized a geentic tool Gjd3-CreEGFP to perform in-depth analysis of AVN structure and composition. Utilizing this AVN-specific mouse model, we performed scRNA-Seq on neonatal Gjd3-CreEGFP mice to guide our single-cell atlas of the Atrio-ventricular conduction system (AVCS).
Using Gjd3-CreEGFP mice to examine atrioventricular node morphology and composition.
Specimen part, Subject
View SamplesZBTB20 is an adjuvant-specific factor for long-term antibody responses. This factor is critical for maintaining long-lived plasma cells in alum-adjuvanted antibody responses but is dispensable for TLR ligand-adjuvanted responses.
Adjuvant-specific regulation of long-term antibody responses by ZBTB20.
Specimen part
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