Mesenchymal stem cells (MSCs) are an essential component of the bone marrow (BM) microenvironment and have shown to support cancer evolution in multiple myeloma (MM). Despite the increasing evidence that MM MSCs differ from their healthy counterparts, little knowledge exists as to whether MSCs independently influence disease outcome. The aim of the present study was to determine the importance of MSCs in disease progression and outcome in MM.
The Pattern of Mesenchymal Stem Cell Expression Is an Independent Marker of Outcome in Multiple Myeloma.
Specimen part, Disease, Subject
View SamplesTo elucidate the mechanisms underlying relapse from chemotherapy in multiple myeloma we performed a longitudinal study of 33 patients entered into Total Therapy protocols investigating them using gene expression profiling, high resolution copy number arrays and whole exome sequencing. The study illustrates the mechanistic importance of acquired mutations in known myeloma driver genes and the critical nature of bi-allelic inactivation events affecting tumor suppressor genes, especially TP53. The end result being resistance to apoptosis and increased proliferation rates, which drive relapse by Darwinian type clonal evolution. The number of copy number aberration changes and bi-allelic inactivation of tumor suppressor genes was increased in GEP70 high risk, consistent with genomic instability being a key feature of high risk. In conclusion, the study highlights the impact of acquired genetic events, which enhance the evolutionary fitness level of myeloma propagating cells to survive multi-agent chemotherapy and to result in relapse.
Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma.
Sex, Specimen part, Disease stage
View SamplesIxodes species ticks are competent vectors of tick-borne viruses including tick-borne encephalitis and Powassan encephalitis. Tick saliva has been shown to facilitate and enhance viral infection. This likely occurs by saliva-mediated modulation of host responses into patterns favorable for viral infection and dissemination. Because of the rapid kinetics of tick-borne viral transmission, this modulation must occur as early as tick attachment and initiation of feeding. In this study, the gene expression profile of cutaneous bite-site lesions created by uninfected ticks were analyzed at 1, 3, 6, and 12 hours after Ixodes scapularis nymphal tick attachment to discover host pathways or responses potentially important in tick-borne viral establishment.
Early immunologic events at the tick-host interface.
Specimen part, Time
View SamplesThe purpose of this study was to determine and clarify the retinoic effect on the gene expression profile for mouse dendritic cells.
Retinoic acid promotes the development of Arg1-expressing dendritic cells for the regulation of T-cell differentiation.
Specimen part
View SamplesTGF is one of most intensively studied regulators of extracellular matrix formation, and has been implicated in the development of pulmonary fibrosis in different models. However, little is know about the role of miRNAs in TGF mediated fibrogenic gene regulation. By using miRNA qRT-PCR array, we have identified miRNAs whose expression are regulated by TGF in IMR-90 cells. Among those down-regulated miRNAs are miR-29 family members. Knockdown miR-29 in IMR-90 cells results in up-regulation of a large number of extracellular matrix and fibrogenic genes including family members of collagen, laminin, integrin, ADAM and MMP, many of them are predicted or confirmed miR-29 targets. Hierarchichal clustering analysis of mRNA array data revealed that many extracellular matrix and fibrogenic genes up-regulated by TGF in IMR-90 cells, are also up-regulated in miR-29 KD cells. Moreover, the similar set of extracellular matrix and fibrogenic genes is also significantly up-regulated in bleomycin treated mouse lungs. Together, our data strongly suggest that downstream of the TGF, miR-29 is a master modulator of genes involved in extracellular matrix formation and might play a significant role in pulmonary fibrosis.
miR-29 is a major regulator of genes associated with pulmonary fibrosis.
Specimen part, Cell line
View SamplesTumor cells have an increased need for amino acids. Mammalian cells cannot synthesize essential amino acids; they must obtain these amino acids via specific transporters. Glutamine, though a non-essential amino acid, is critical for tumor cells (glutamine addiction). Entry of amino acids into tumor cells is enhanced by upregulation of specific transporters. If the transporters that are specifically induced in tumor cells are identified, blockade of the induced transporters would constitute a logical strategy for cancer treatment.
Deletion of the amino acid transporter Slc6a14 suppresses tumour growth in spontaneous mouse models of breast cancer.
Age, Specimen part
View SamplesWe have carried out transcriptional profile analysis in macroH2A knockdown cells (Namalwa B cells and HeLa cells) and demonstrated that this histone variant plays positive and negative roles in transcription. We also demonstrated the role of macroH2A in regulating the response to Sendai Virus infection.
Composite macroH2A/NRF-1 Nucleosomes Suppress Noise and Generate Robustness in Gene Expression.
Cell line, Treatment
View SamplesSTAT5 interacts with other factors to control transcription, and the mechanism of regulation is of interest as constitutive active STAT5 has been reported in malignancies. Here LSD1 and HDAC3 were identified as novel STAT5a interacting partners in pro-B cells. Characterization of STAT5a, LSD1 and HDAC3 target genes by ChIP-seq and RNA-seq revealed gene subsets regulated by independent or combined action of the factors and LSD1/HDAC3 to play dual role in their activation or repression. Genes bound by STAT5a alone or in combination with weakly associated LSD1 or HDAC3 were enriched for the canonical STAT5a dimer motif, and such binding induced activation or repression. Strong STAT5 binding was seen more frequently in intergenic regions, which might function as distal enhancer elements. Genes bound weakly by STAT5a and strongly by LSD1/HDAC3 present a STAT5a monomer like motif, and are differentially regulated based on their biological role, genomic binding localization and affinity. STAT5a binding in monomer like motifs was found with increased frequency in promoters, indicating a requirement for stabilization by additional factors, which might recruit LSD1/HDAC3. Our study describes an interaction network of STAT5a/LSD1/HDAC3 and a dual function of LSD1/HDAC3 on STAT5-dependent transcription, defined by protein-protein interactions, genomic binding positions-affinities and motifs. Overall design: Mouse pro-B Ba/F3 cells treated with lentiviral vectors expressing short-hairpins to knock-down various genes (STAT5a, STAT5b, LSD1 and HDAC3). All KDs were analysed versus cells treated with lentiviral construct expressing a No-Target short-hairpin at the same condition (either minus [IL3 deprivation for 6h] or plus [IL3 deprivation for 6h and IL3 stimulation for 30min]). Wild-type cells were also generated and compared between the two conditions. All samples contain biological replicates (3-5 depending on the sample).
The dual role of LSD1 and HDAC3 in STAT5-dependent transcription is determined by protein interactions, binding affinities, motifs and genomic positions.
Cell line, Treatment, Subject
View SamplesWe applied next-generation sequencing to investigate the gene expression profiles in mouse bone-marrow derived macrophages with or without long noncoding RNA-Malat1 knockdown. We identified a number of differentially regulated genes in cells with Malat1 knockdown. Overall design: Mouse bone-marrow derived macrophages were transfected with Antisense LNAâ„¢ GapmeRs against Malat1 or Negative Control oligos (Exiqon). 48h after transfection, total RNA was isolated and subjected to high-throughput sequencin (RNA-seq), using Illumina GAIIx. Gene expression profiles were compared between two groups.
Long noncoding RNA Malat1 regulates differential activation of macrophages and response to lung injury.
Specimen part, Cell line, Subject
View SamplesThis is the expression dataset for two studies: 1) Characterization of visceral and subcutaneous adipose tissue transcriptome and biological pathways in pregnant and non-pregnant women: Evidence for pregnancy-related regional-specific differences in adipose tissue and 2) Characterization of visceral and subcutaneous adipose tissue transcriptome in pregnant women with and without spontaneous labor at term: Implication of alternative splicing in the metabolic adaptations of adipose tissue to parturition.
Characterization of visceral and subcutaneous adipose tissue transcriptome in pregnant women with and without spontaneous labor at term: implication of alternative splicing in the metabolic adaptations of adipose tissue to parturition.
Specimen part, Disease stage, Subject
View Samples