The ubiquitin proteasome system (UPS) is known to possess important regulatory functions in the immune response. To gain a better and first comprehensive insight into the mechanisms underlying the conversion of immature to mature DC in terms of the expression of UPS related genes, we undertook a comparative gene expression profiling during DC maturation in response to four different prototypic maturation stimuli.
Maturation of human dendritic cells is accompanied by functional remodelling of the ubiquitin-proteasome system.
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View SamplesThe cellular origin of chronic lymphocytic leukemia (CLL) is debated. Transcriptome analysis of CLL and normal peripheral blood and splenic B cell subsets displayed highest similarity of CLL to mature CD5+ B cells. We identified a distinct CD5+CD27+ post-germinal center B cell subset, and revealed that immunoglobulin V gene mutated CLL are more similar to mutated CD5+ B cells, whereas unmutated CLL are more related to unmutated CD5+ B cells. Stereotyped immunoglobulin V gene rearrangements were significantly enriched among CD5+ B cells, providing further genetic evidence for a derivation of CLL from CD5+ B cells. Moreover, we identified deregulated expression patterns providing novel insights into the pathophysiology of CLL, including downregulation of EBF1 and KLF family members.
Cellular origin and pathophysiology of chronic lymphocytic leukemia.
Specimen part
View SamplesAim of this project was to determine the transcriptional response of the isolate PA30 to tap water and waste water.
Whole genome and transcriptome analyses of environmental antibiotic sensitive and multi-resistant Pseudomonas aeruginosa isolates exposed to waste water and tap water.
Specimen part
View SamplesAim of this project was to determine the transcriptional response of the isolate PA49 to tap water and waste water.
Whole genome and transcriptome analyses of environmental antibiotic sensitive and multi-resistant Pseudomonas aeruginosa isolates exposed to waste water and tap water.
Specimen part
View SamplesGenome wide gene expression profile of the lrx1 root hair mutant and the suppressor mutations lrx1 rol1-1 and lrx1 rol1-2.
The Arabidopsis root hair cell wall formation mutant lrx1 is suppressed by mutations in the RHM1 gene encoding a UDP-L-rhamnose synthase.
Age, Specimen part
View SamplesLower urinary tract malformations are among the most common congenital anomalies in humans. The urethral plate epithelium is an endodermal signaling region that plays an essential role in external genital development; however, little is known about the molecular identity of this cell population or the genes that regulate its activity. We aim to characterize differences in gene expression between the urethral plate epithelium and surrounding mouse genital tubercles during a crucial developmental period.
Molecular Characterization of the Genital Organizer: Gene Expression Profile of the Mouse Urethral Plate Epithelium.
Sex, Specimen part
View SamplesThe Drosophila piRNA pathway provides an RNA-based immune system that defends the germline genome against selfish genetic elements. Two inter-related branches of the piRNA system exist: somatic cells that support oogenesis only employ Piwi, whereas germ cells utilize a more elaborated pathway centered on the three gonad-specific Argonaute proteins Piwi, Aubergine, and Argonaute3. While several key factors of each branch have been identified, our current knowledge is insufficient to explain the complex workings of the piRNA machinery. Here, we report a reverse genetic screen spanning the ovarian transcriptome in an attempt to uncover the full repertoire of genes required for piRNA-mediated transposon silencing in the female germline. Our screen reveals new key factors of piRNA-mediated transposon silencing, including the novel piRNA biogenesis factors, CG2183 (GASZ) and Deadlock. Last, our data uncovers a previously unanticipated set of factors preferentially required for repression of different transposons types. Overall design: Examination of total RNA levels from nos-GAL4 or tj-GAL4 driven UAS-dsRNA knockdowns of control genes and piRNA pathway components in ovaries of Drosophila melanogaster by deep sequencing (using Illumina HiSeq2000).
Regulation of Ribosome Biogenesis and Protein Synthesis Controls Germline Stem Cell Differentiation.
Specimen part, Subject
View SamplesThe Drosophila piRNA pathway provides an RNA-based immune system that defends the germline genome against selfish genetic elements. Two inter-related branches of the piRNA system exist: somatic cells that support oogenesis only employ Piwi, whereas germ cells utilize a more elaborated pathway centered on the three gonad-specific Argonaute proteins Piwi, Aubergine, and Argonaute3. While several key factors of each branch have been identified, our current knowledge is insufficient to explain the complex workings of the piRNA machinery. Here, we report a reverse genetic screen spanning the ovarian transcriptome in an attempt to uncover the full repertoire of genes required for piRNA-mediated transposon silencing in the female germline. Our screen reveals new key factors of piRNA-mediated transposon silencing, including the novel piRNA biogenesis factors, CG2183 (GASZ) and Deadlock. Last, our data uncovers a previously unanticipated set of factors preferentially required for repression of different transposons types. Overall design: Examination of small RNA levels from nos-GAL4 or tj-GAL4 driven UAS-dsRNA knockdowns of control genes and piRNA pathway components in ovaries of Drosophila melanogaster by deep sequencing (using Illumina HiSeq2000).
Regulation of Ribosome Biogenesis and Protein Synthesis Controls Germline Stem Cell Differentiation.
Specimen part, Subject
View SamplesSmall subsets of B cells in the germinal center (GC) and in extrafollicular regions of lymph nodes express the activation marker CD30. Very little is known about the specific features of these cells and their relationship to the CD30-expressing Hodgkin and Reed/Sternberg (HRS) cells of Hodgkin lymphoma. Phenotypic and immunoglobulin V gene analyses revealed that CD30+ GC B lymphocytes represent typical GC B cells, and that CD30+ non-GC B cells are mostly post-GC B cells. However, despite these seemingly distinct identities, both CD30+ subsets share an unexpectedly large overlap in specific transcriptome patterns, and are strikingly different from bulk GC B cells and classical memory and plasma cells, respectively. A main common feature of these CD30+ B cells is a strong MYC signature. CD30+ GC B cells appear to represent the recently described MYC+ GC B cell subset of recirculating centrocytes at the stage of centroblast transition. CD30+ non-GC B cells rather represent highly activated and proliferating memory B cells, differentiating into plasma cells. Notably, CD30+ B cells were more similar in their transcriptome patterns to HRS cells than any other B cell subset investigated, suggesting that HRS cells may either derive from CD30+ B cells or acquired a similar activation signature. In comparison to CD30+ B cells and other lymphomas, HRS cells show a remarkable downregulation of genes regulating cell cycle, genomic stability and polyploidity, providing a potential explanation for the genomic instability and multinuclearity of HRS cells.
Human CD30+ B cells represent a unique subset related to Hodgkin lymphoma cells.
Specimen part
View SamplesEfficient processing of target antigens by the ubiquitin-proteasome-system (UPS) is essential for treatment of cancers by T cell therapies. However, immune escape due to impaired expression of IFN--inducible components of the antigen presentation machinery and consequent inefficient processing of HLA-dependent tumor epitopes can be one important reason for failure of such therapies. Here, we show that repeated short-term co-cultures of Melan-A/MART-1 tumor antigen-expressing melanoma cells with Melan-A/MART-1 (26-35)-specific CTL led to the generation of clones resistant to CTL-mediated cell death. To determine which of the UPS components and its associated pathways was responsible for CTL escape; three UKRV-Mel-15a clones were subjected to microarray gene expression analysis.
Exposure to Melan-A/MART-126-35 tumor epitope specific CD8(+)T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS).
Specimen part
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