This series represent several subgroups of experiments designed to investigate the role of basal immunoglobulin signaling in immature B cell development. The first subgroup of arrays (Ctrl Mhi, Cre Mhi, Cre Mlo) was done to identify the changes in gene expression in immature B cells as a consequence of inducible deletion of surface IgM expression via Cre-LoxP mediated excision of Ig heavy chain. The second subgroup of arrays (GFPneg, GFPpos, FxE Ctrl, FxE HA) was done to identify the changes in gene expression in immature B cells as a consequence of blockade of tyrosine kinase signaling with herbimycin A treatment. The third subgroup of arrays (FxD, FxE, B6 Mneg, HEL Mhi) was done to establish gene expression profiles of immature B, pre B and pro B cells as reference platforms for the other two subgroups. (Tze etal. Public Library of Science Biology, 2005)
Basal immunoglobulin signaling actively maintains developmental stage in immature B cells.
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View SamplesThe neural transcription factor SOX11 is overexpressed in aggressive lymphoid neoplasms mainly in mantle cell lymphoma (MCL). We have recently demonstrated SOX11 tumorigenic potential in vivo by showing a significant reduction on tumor growth of SOX11-knockdown MCL cells in xenograft experiments, confirming the clinical observations that SOX11 may play an important role in the aggressive behavior of MCL (Vegliante et al., 2013). However, the specific mechanisms regulated by SOX11 that promote the oncogenic and rapid tumor growth of aggressive MCL still remain to be elucidated. To further characterize the potential oncogenic mechanisms regulated by SOX11 in MCL, we have analyzed the GEP derived from the xenograft SOX11-positive and knockdown xenograft derived tumors.
SOX11 promotes tumor angiogenesis through transcriptional regulation of PDGFA in mantle cell lymphoma.
Specimen part
View SamplesThe neural transcription factor SOX11 is overexpressed in aggressive lymphoid neoplasms mainly in mantle cell lymphoma (MCL), but its functional role in malignant B-cells is unknown. To identify target genes transcriptionally regulated by SOX11 in malignant lymphoid cells, we have used Gene Expression Profiling (GEP) after SOX11 silencing in MCL cell lines.
SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma.
Specimen part, Cell line
View SamplesNeuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia. There is no evidence of this type of pain in human infants or rat pups; brachial plexus avulsion, which causes intense neuropathic pain in adults, is not painful when the injury is sustained at birth. Since infants are capable of nociception from before birth and display both acute and chronic inflammatory pain behaviour from an early neonatal age, it appears that the mechanisms underlying neuropathic pain are differentially regulated over a prolonged postnatal period.
Differential regulation of immune responses and macrophage/neuron interactions in the dorsal root ganglion in young and adult rats following nerve injury.
Specimen part
View SamplesTo understand the fruit changes and mechanisms involved in the compatible grapevine-virus interaction, we analyzed the berry transcriptome in two stages of development (veraison and ripening) in the red wine cultivar Cabernet Sauvignon infected with Grapevine leaf-roll-associated virus-3 (GLRaV-3). Analysis of global gene expression patterns indicate incomplete berry maturation in infected berries as compared to uninfected fruit suggesting viral infection interrupts the normal berry maturation process.
Compatible GLRaV-3 viral infections affect berry ripening decreasing sugar accumulation and anthocyanin biosynthesis in Vitis vinifera.
Age, Specimen part
View SamplesPlant growth promoting rhizobacteria (PGPR) induce positive effects in plants, such as increased growth or reduced stress susceptibility. The mechanisms behind PGPR/plant interaction are poorly understood, as most studies have described short- term responses on plants and only a few studies have analyzed plant molecular responses under PGPR colonization.
Effects of the plant growth-promoting bacterium Burkholderia phytofirmans PsJN throughout the life cycle of Arabidopsis thaliana.
Specimen part, Time
View SamplesBoron is an essential micronutrient for plants and is taken up in the form of boric acid (BA). Despite this, a high BA concentration is toxic for the plants, inhibiting root growth and is thus a significant problem in semi-arid areas in the world. In this work, we report the molecular basis for the inhibition of root growth caused by boron. We used microarrays to detail the global gene expression underlying boron toxicity in roots.
A molecular framework for the inhibition of Arabidopsis root growth in response to boron toxicity.
Specimen part, Treatment
View SamplesGene expression analyis of primary MCL including IGHV mutated and unmutated cases
Molecular subsets of mantle cell lymphoma defined by the IGHV mutational status and SOX11 expression have distinct biologic and clinical features.
Specimen part, Disease, Disease stage
View SamplesMammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a critical regulator of cell growth by integrating multiple signals (nutrients, growth factors, energy and stress) and is frequently deregulated in many types of cancer. We used a robust experimental paradigm involving the combination of two interventions, one genetic and one pharmacologic to identify genes regulated transcriptionally by mTORC1. In Tsc2+/+, but not Tsc2-/- immortalized mouse embryo fibroblasts (MEFs), serum deprivation downregulates mTORC1 activity. In Tsc2-/- cells, abnormal mTORC1 activity can be downregulated by treatment with rapamycin (sirolimus). By contrast, rapamycin has little effect on mTORC1 in Tsc2+/+ cells in which mTORC1 is already inhibited by low serum. Thus, under serum deprived conditions, mTORC1 activity is low in Tsc2+/+ cells (untreated or rapamycin treated), high in Tsc2-/- cells, but lowered by rapamycin; a pattern referred to as a low/low/high/low or LLHL, which allowed the identification of genes regulated by mTORC1 by performing the appropriate comparisons
Regulation of TFEB and V-ATPases by mTORC1.
Specimen part, Treatment
View SamplesHistone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL). We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL). To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM) model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (E). Here, we report that the E-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD) with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of E-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors.
Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice.
Specimen part
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