Our studies identify the role of mIR-28 in germinal center response and its therapeutic potential for the treatment of non-Hodgkin lymphomas Overall design: The effect of miR-28 expression in the transcriptome was analyzed in Ramos Burkitt B cells by RNASeq.
miR-28 regulates the germinal center reaction and blocks tumor growth in preclinical models of non-Hodgkin lymphoma.
Treatment, Subject
View SamplesWe have characterized a mutation affecting the Arabidopsis EARLY IN SHORT DAYS 7 (ESD7) gene encoding the catalytic subunit of the DNA polymerase epsilon (e), AtPOL2A. esd7-1 mutations causes early flowering independently of photoperiod, shortened inflorescence internodes and altered leaf and root development. esd7-1 was a hypomorphic allele whereas KO alleles displayed an embryo-lethal phenotype. The SAM and the RAM in the esd7-1 seedlings were found to exhibit an altered disposition that might correlate with the abnormal expression pattern of SAM and RAM marker genes. esd7-1 showed higher sensitivity to DNA damaging reagents than wild type plants and altered expression of genes involved in DNA repair mechanisms by homologous recombination. Moreover, esd7 early flowering phenotype requires functional FT and SOC1 proteins and might be also related to the mis-regulation of AG and AG-like gene expression found in esd7. Loci involved in the modulation of the chromatin structural dynamics, such as TFL2 and EBS, which negatively regulate FT expression, were found to interact genetically with ESD7, and the carboxy terminus of ESD7 interacted with TFL2 in vitro. Besides, fasciata2 (fas2) mutations suppressed esd7 early flowering phenotype and INCURVATA 2 (ICU2) was found to be epistatic to ESD7. Discrete regions of the chromatin of FT and AG loci were enriched in activating epigenetic marks in the esd7-1 mutant. We concluded that ESD7 might be participating in processes involved in chromatin-mediated cellular memory.
EARLY IN SHORT DAYS 7 (ESD7) encodes the catalytic subunit of DNA polymerase epsilon and is required for flowering repression through a mechanism involving epigenetic gene silencing.
Specimen part
View SamplesTrisomy 21 (Ts21) or Down syndrome (DS) is the most common genetic cause of intellectual disability. To investigate the consequences of Ts21 on human brain development, we have systematically analyzed the transcriptome of dorsolateral prefrontal cortex (DFC) and cerebellar cortex (CBC) using exon array mapping in DS and matched euploid control brains spanning from prenatal development to adulthood. We identify hundreds of differentially expressed (DEX) genes in the DS brains, many of which exhibit temporal changes in expression over the lifespan. To gain insight into how these DEX genes may cause specific DS phenotypes, we identified functional modules of co-expressed genes using several different bioinformatics approaches, including WGCNA and gene ontology analysis. A module comprised of genes associated with myelination, including those dynamically expressed over the course of oligodendrocyte development, was amongst those with the great levels of differential gene expression. Using Ts65Dn mouse line, the most common rodent model of DS, w e observed significant and novel defects in oligodendrocyte maturation and myelin ultrastructure; establishing a correlative proof-of-principle implicating myelin dysgenesis in DS. Thus, examination of the spatio-temporal transcriptome predicts specific cellular and functional events in the DS brain and is an outstanding resource for determining putative mechanisms involved in the neuropathology of DS.
Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination.
Sex, Disease, Race
View SamplesExamining the transcriptomic changes during transdifferentiation of peripheral blood mononuclear cells to induced neuronal cells. Overall design: There are three different populations: PBMC (2 biological replicates, starting population), PSA-NCAM+GFP+ (2 biological replicates, induced neuronal cells) and PSA-NCAM+GFP- (2 biological replicates, induced neuronal cells).
Transdifferentiation of human adult peripheral blood T cells into neurons.
Specimen part, Subject
View SamplesNeuroblastoma is an embryonal neoplasm that remains of dramatic prognosis in its aggressive forms. Activating mutations of the ALK tyrosine kinase receptor have been identified in sporadic and familial cases of this cancer. We generated knock-in mice carrying the two most frequent Alk mutations observed in neuroblastoma patients. We used microarrays to detail the global programme of gene expression underlying the impact of ALK mutations on neuroblastoma formation in a MYCN amplified background.
Activated Alk triggers prolonged neurogenesis and Ret upregulation providing a therapeutic target in ALK-mutated neuroblastoma.
Specimen part
View SamplesWe report here the genes that are sequentially expressed in white blood cells from blood and spleen at 2 hours, 2 day,3 days, and 7 days after burn and sham injury or trauma-hemorrhage (T-H) and sham T-H. Includes WBC treated with LPS for 2 hours and 1 day.
Comparison of longitudinal leukocyte gene expression after burn injury or trauma-hemorrhage in mice.
Specimen part, Treatment, Time
View SamplesThe liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DC), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migration in vitro and in vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished LXR-dependent induction of DC chemotaxis. Using the LDLR-/- mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for efficient emigration of DCs in response to chemotactic signals during inflammation.
LXR nuclear receptors are transcriptional regulators of dendritic cell chemotaxis.
Specimen part
View SamplesMouse BMDCs were differentiated from bone marrow by GM-CSF and IL-4 for 9 days.
LXR nuclear receptors are transcriptional regulators of dendritic cell chemotaxis.
Specimen part
View SamplesBackground: Inter-patient prostate cancer (PrCa) heterogeneity results in highly variable patient outcomes. Multi-purpose biomarkers to dissect this heterogeneity are urgently required to improve treatment and accelerate drug development in PrCa. Circulating biomarkers are most practical for evaluating this disease. We pursued the analytical validation and clinical qualification of blood mRNA expression arrays.
Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: a prospective, two-stage study.
Subject
View SamplesEthnically diverse - African American, Hispanic Latino, Asian - induced pluripotent stem cell lines bioinformatics data
Derivation of Ethnically Diverse Human Induced Pluripotent Stem Cell Lines.
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