SPC2996 is a novel locked nucleic acid (LNA) phosphorothioate antisense molecule targeting the mRNA of the Bcl-2 oncoprotein. We investigated the mechanism of action of SPC2996 and the basis for its clinically observed immunostimulatory effects in chronic lymphocytic leukemia (CLL). Patients with relapsed CLL were treated with a maximum of six doses of SPC2996 (0.2-6mg/ kg) in a multicenter phase I trial. Microarray-based transcriptional profiling of circulating CLL cells was carried out before and after the first infusion of SPC2996 in eighteen patients.
The novel antisense Bcl-2 inhibitor SPC2996 causes rapid leukemic cell clearance and immune activation in chronic lymphocytic leukemia.
Specimen part, Time
View SamplesSaccharomyces cerevisiae IMS0002 which, after metabolic and evolutionary engineering, ferments the pentose sugar arabinose. Glucose and arabinose-limited anaerobic chemostat cultures of IMS0002 and its non-evolved ancestor IMS0001 were subjected to transcriptome analysis to identify key genetic changes contributing to efficient arabinose utilization by strain IMS0002.
Metabolome, transcriptome and metabolic flux analysis of arabinose fermentation by engineered Saccharomyces cerevisiae.
Disease, Treatment
View SamplesThis study aimed to identify genes that are linked with optineurin expression using a combined siRNA-microarray approach
Identification of genes that are linked with optineurin expression using a combined RNAi--microarray approach.
No sample metadata fields
View SamplesDrosophila melanogaster neural stem cells (neuroblasts [NBs]) divide asymmetrically by differentially segregating protein determinants into their daughter cells. Although the machinery for asymmetric protein segregation is well understood, the events that reprogram one of the two daughter cells toward terminal differentiation are less clear. In this study, we use time-resolved transcriptional profiling to identify the earliest transcriptional differences between the daughter cells on their way toward distinct fates. By screening for coregulated protein complexes, we identify vacuolar-type H+–ATPase (v-ATPase) among the first and most significantly down-regulated complexes in differentiating daughter cells. We show that v-ATPase is essential for NB growth and persistent activity of the Notch signaling pathway. Our data suggest that v-ATPase and Notch form a regulatory loop that acts in multiple stem cell lineages both during nervous system development and in the adult gut. We provide a unique resource for investigating neural stem cell biology and demonstrate that cell fate changes can be induced by transcriptional regulation of basic, cell-essential pathways. Overall design: Comparison of transcriptomes of wild-type type I NBs and GMCs of different ages (1.5h, 3h or 5h old) isolated by FACS from Drosophila melanogaster larval brains.
Time-resolved transcriptomics in neural stem cells identifies a v-ATPase/Notch regulatory loop.
Specimen part, Subject
View SamplesNoncommunicable chronic respiratory diseases (CRDs) such as chronic obstructive pulmonary disease (COPD) and asthma affect hundreds of millions of people and are associated with increasing morbidity and mortality. CRDs are multifactorial disorders and despite different etiologies they commonly manifest in pulmonary structural (airway remodeling, emphysema) and/or functional changes. In this study we used mice intrinsically developing autoimmune-mediated lung inflammation associated with lung pathology and immune imprinting partly comparable to hallmarks of CRD. The so called SPC-HAxTCR-HA transgenic mice (BALB/c genetic background), express a neo-self antigen (influenza A virus hemagglutinin, HA) on lung alveolar epithelial type II cells in the presence of HA-specific CD4+ T cells leading to the establishment of chronic lung inflammation. In order to characterize the inflammatory lung milieu of SPC-HAxTCR-HA mice in comparison to SPC-HA control mice (lacking HA-specific CD4+ T cells), we performed whole lung tissue transcriptional analyses (n = 3 / group). 378 transcripts were found to be differentially expressed in SPC-HAxTCR-HA lungs. 326 of those were up-regulated and 52 were down-regulated compared to SPC-HA control mice.
Chronic lung inflammation primes humoral immunity and augments antipneumococcal resistance.
Sex, Age, Specimen part
View SamplesMice lacking the zinc finger transcription factor Specificity protein 3 (Sp3) die prenatally in the C57Bl/6 background. To elucidate the cause of mortality we analyzed the potential role of Sp3 in embryonic heart development. Sp3 null hearts display defective looping at E10.5, and at E14.5 the Sp3 null mutants have developed a range of severe cardiac malformations. In an attempt to position Sp3 in the cardiac developmental hierarchy, we analysed the expression patterns of >15 marker genes in Sp3 null hearts. Expression of Cardiac ankyrin repeat protein (Carp) was downregulated prematurely after E12.5, while expression of the other marker genes was not affected. ChIP analysis revealed that Sp3 is bound to the Carp promoter region in vivo. Microarray analysis indicates that small molecule metabolism and cell-cell interactions are the most significantly affected biological processes in E12.5 Sp3 null myocardium. Since the epicardium showed distension from the myocardium, we studied expression of Wt1, a marker for epicardial cells. Wt1 expression was diminished in epicardium-derived cells in the myocardium of Sp3 null hearts. We conclude that Sp3 is required for normal cardiac development, and suggest that it has a crucial role in myocardial differentiation. (
Transcription factor Sp3 knockout mice display serious cardiac malformations.
No sample metadata fields
View SamplesWe generated chimeric mice with livers that were predominantly repopulated with human hepatocytes. Hepatocytes were isolated from the chimeric mouse livers and their gene expressions were compared with hepatocytes isolated from normal human livers . Cluster and principal components analyses showed that gene expression profiles of hepatocytes from the chimeric mice and those from normal human livers were extremely closed.
Morphological and microarray analyses of human hepatocytes from xenogeneic host livers.
Sex, Age, Specimen part, Race
View SamplesWe performed microarray experiments to examine gene expression in human tissues. This data was used for comparison with our humanized mouse study (GEO ID GSE33846) and threshold determination of our tiling array data (GEO ID GSE18490, public in the near future).
Morphological and microarray analyses of human hepatocytes from xenogeneic host livers.
Specimen part, Cell line, Race
View SamplesNeonates are intrinsically defective at creating memory CD8+ T cells in response to infection with intracellular pathogens. Here we investigated differential of small RNAs, transcription factors, and chemokine receptors regulation in neonates as compared to adults before and during infection. We found that prior to infection, na誰ve cells have a different expression profile for many microRNAs, and gene targets of these microRNAs show widespread expression differences. These targets and other changes in gene expression in na誰ve cells result in neonatal cells that get activated more easily, express chemokine receptors that home to sites of infection, and are less protected from apoptosis during contraction. As a result, changes in neonatal na誰ve cells drive effector cell terminal differentiation at the expense of creating long-lived memory cells. Overall design: total RNAs were sequenced from adult and neonatal CD8+ T cells before and during infection
MicroRNAs and Their Targets Are Differentially Regulated in Adult and Neonatal Mouse CD8+ T Cells.
No sample metadata fields
View SamplesNeonates are intrinsically defective at creating memory CD8+ T cells in response to infection with intracellular pathogens. Here we investigated differential of small RNAs, transcription factors, and chemokine receptors regulation in neonates as compared to adults before and during infection. We found that prior to infection, na誰ve cells have a different expression profile for many microRNAs, and gene targets of these microRNAs show widespread expression differences. These targets and other changes in gene expression in na誰ve cells result in neonatal cells that get activated more easily, express chemokine receptors that home to sites of infection, and are less protected from apoptosis during contraction. As a result, changes in neonatal na誰ve cells drive effector cell terminal differentiation at the expense of creating long-lived memory cells. Overall design: PolyA RNA was selected and sequenced from adult and neonatal CD8+ T cells before and during infection
MicroRNAs and Their Targets Are Differentially Regulated in Adult and Neonatal Mouse CD8+ T Cells.
No sample metadata fields
View Samples