This SuperSeries is composed of the SubSeries listed below.
Clonal competition with alternating dominance in multiple myeloma.
Specimen part
View SamplesCopy number and expression profiling of multiple myeloma patients at multiple stages of their individual clinical course
Clonal competition with alternating dominance in multiple myeloma.
Specimen part
View SamplesMultiple myeloma is a relatively common B-cell malignancy that is currently incurable. Certain recurrent genetic abnormalities characteristics of different genetic subtypes have been described. Hyperdiploid myeloma characterized by recurrent trisomies is the most common genetic subtypes. However little is know about it's biology. Another common genetic abnormality is chromosome 13 deletion which is also associated with inferior prognosis. This abnormality is already present at the pre-malignant MGUS stage and is clonally selected with disease progression. Although it is biologically and clinically important the molecular consequence of chromosome 13 deletion is unknown.
Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling.
No sample metadata fields
View SamplesEstrogen-Related Receptor alpha (ERR) is a nuclear receptor that acts principally as a regulator of metabolism processes particularly in tissues subjected to high-energy demand. Besides its implication in energy metabolism and mitochondrial biogenesis, ERR was recently associated with tumorigenesis. Notably, increased expression of ERR was noted in different cancerous tissues as breast, ovary and colon. However, supplemental studies are required to better understand the role of ERR in colon carcinoma.
ERRĪ± metabolic nuclear receptor controls growth of colon cancer cells.
Cell line, Treatment
View SamplesWaldenstrms macroglobulinemia (WM) is a distinct clinicobiological entity defined as a B-cell neoplasm characterized by a lymphoplasmacytic infiltrate in the bone marrow and immunoglobulin M paraprotein production. Cytogenetic analysis is limited by the difficulty in obtaining tumor metaphases and the genetic basis of the disease remains poorly defined. We performed a comprehensive analysis in 42 WM patients by using high-resolution array-based comparative genomic hybridization with the Human Genome 244A microarray. Overall, 83% of samples have chromosomal abnormalities, with a median of three abnormalities per patient (range 0 to 27). The most common abnormality was 6q deletion (40%) and four non-overlapped minimal deleted regions (MDR) were identified. Gain of 6p was the second most common abnormality (17%) and its presence was always concomitant with 6q loss. An interstitial MDR was delineated at 13q14 including MIRN15A and MIRN16-1 in 10% of patients. Other recurrent deletions were 7q22, 8p, 11q22-q23, 11q23-q24 and 17p11-p13 (7% each). Copy gains were identified in chromosomes 18 (17%), 4 (12%), 3 (10%), 8q (10%) and Xq27.1-q28 (10%). To note, we reported biallelic deletions and/or inactivating mutations with uniparental disomy in TRAF3 and TNFAIP3, two negative regulators of the NF-kB signaling pathway. Furthermore, we confirmed the association between TRAF3 inactivation and increased transcriptional activity of NF-kB target genes. Mutational activation of the NF-kB pathway, which is normally activated by ligand-receptor interactions within the bone marrow microenvironment, highlight its biologic importance, and suggest a therapeutic role for inhibitors of NF-KB pathway activation in the treatment of Waldenstrms macroglobulinemia.
Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom's macroglobulinemia.
Sex, Age, Specimen part
View SamplesZinc (Zn2+) is an integral component of many proteins and has been shown to act in a regulatory capacity in different mammalian systems, including as a neurotransmitter in neurons throughout the brain. While Zn2+ plays an important role in modulating neuronal potentiation and synaptic plasticity, little is known about the signaling mechanisms of this regulation. In dissociated rat hippocampal neuron cultures, we used fluorescent Zn2+ sensors to rigorously define resting Zn2+ levels and stimulation-dependent intracellular Zn2+ dynamics, and we performed RNA-Seq to characterize Zn2+-dependent transcriptional effects upon stimulation. We found that relatively small changes in cytosolic Zn2+ during stimulation altered expression levels of 931 genes, and these Zn2+ dynamics induced transcription of many genes implicated in neurite expansion and synaptic growth. Additionally, while we were unable to verify the presence of synaptic Zn2+ in these cultures, we did detect the synaptic vesicle Zn2+ transporter ZnT3 and found it to be substantially upregulated by cytosolic Zn2+ increases. These results provide the first global sequencing-based examination of Zn2+-dependent changes in transcription and identify genes that may mediate Zn2+-dependent processes and functions. Overall design: 3 replicates of each of 3 conditions (KCl treatment, KCl/Zn treatment, KCl/TPA treatment), none of which are control conditions. KCl treatment was used as the reference condition for all comparisons. TPA = tris(2-pyridylmethyl)amine, a Zn2+ chelator.
Intracellular Zn<sup>2+</sup> transients modulate global gene expression in dissociated rat hippocampal neurons.
Specimen part, Cell line, Treatment, Subject
View SamplesUntreated HIV-1 infection progresses through acute and asymptomatic stages to AIDS. While each of the three stages has well-known clinical, virologic and immunological characteristics, much less is known of the molecular mechanisms underlying each stage. Here we report lymphatic tissue microarray analyses revealing for the first time stage-specific patterns of gene expression during HIV-1 infection. We show that while there is a common set of key genes with altered expression throughout all stages, each stage has a unique gene-expression signature. The acute stage is most notably characterized by increased expression of hundreds of genes involved in immune activation, innate immune defenses (e.g.MDA-5, TLR-7 and -8, PKR, APOBEC3B, 3F, 3G), adaptive immunity, and in the pro-apoptotic Fas-Fas-L pathway. Yet, quite strikingly, the expression of nearly all acute-stage genes return to baseline levels in the asymptomatic stage, accompanying partial control of infection. In the AIDS stage, decreased expression of numerous genes involved in T cell signaling identifies genes contributing to T cell dysfunction. These common and stage-specific, gene-expression signatures provide new insights into the molecular mechanisms underlying the host response and the slow, natural course of HIV-1 infection.
Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection.
Sex, Age, Specimen part, Disease, Disease stage, Race, Subject
View SamplesDuring embryogenesis, cell specification and tissue formation is directed by the concentration and temporal presentation of morphogens, and similarly, pluripotent embryonic stem cells differentiate in vitro into various phenotypes in response to morphogen treatment. Embryonic stem cells are commonly differentiated as three dimensional spheroids called embryoid bodies (EBs); however, differentiation within EBs is typically heterogeneous and disordered. Here we show that spatiotemporal control of microenvironmental cues embedded directly within EBs enhances the homogeneity, synchrony and organization of differentiation. Degradable polymer microspheres releasing retinoic acid within EBs induce the formation of cystic spheroids closely resembling the early streak mouse embryo, with an exterior of visceral endoderm enveloping an epiblast layer. These results demonstrate that controlled morphogen presentation to stem cells more efficiently directs cell differentiation and tissue formation, thereby improving developmental biology models and enabling the development of regenerative medicine therapies and cell diagnostics.
Homogeneous and organized differentiation within embryoid bodies induced by microsphere-mediated delivery of small molecules.
No sample metadata fields
View SamplesChlamydia trachomatis is an obligate intracellular pathogen that causes trachoma and sextually transmitted disease in human. During early stage of infection, Chlamydia secreted bacterial effector proteins into host cell cytoplasm to help its entry and estabilishment of early replicated niche.
The Chlamydia trachomatis type III secretion chaperone Slc1 engages multiple early effectors, including TepP, a tyrosine-phosphorylated protein required for the recruitment of CrkI-II to nascent inclusions and innate immune signaling.
Specimen part, Cell line, Time
View SamplesWnt signaling in early eye development, specifically the lens placode shows expression of 12 out of 19 Wnt ligands. We these Wnt activities were suppressed using conditional deletion of Wntless, dramatic phenotypic changes in morphogensis occurred.
Wnt ligands from the embryonic surface ectoderm regulate 'bimetallic strip' optic cup morphogenesis in mouse.
Specimen part
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