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Mus musculus, Homo sapiens
15 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The pathways regulating the formation of the germinal center (GC) dark- (DZ) and light- (LZ) zones are unknown. We show that FOXO1 expression is restricted to the GC DZ and is required for DZ formation, since its absence in mice leads to the complete loss of DZ gene programs and the formation of LZ-only GCs. FOXO1-negative GC B-cells display normal somatic hypermutation, but defective affinity maturation and class switch recombination. The function of FOXO1 in sustaining the DZ program involves the transactivation of the chemokine receptor CXCR4, and the cooperation with BCL6 in the trans-repression of genes involved in immune activation, DNA-repair and plasma cell differentiation. These results have also implications for understanding the role of FOXO1 mutations in lymphomagenesis.
Publication Title
The FOXO1 Transcription Factor Instructs the Germinal Center Dark Zone Program.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarrays of gene expression in human germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4
Publication Title
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarrays of gene expression in mouse germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4
Publication Title
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Germinal centers (GC) arise within B cell follicles upon antigenic challenge. In the dark zones (DZ) of GCs, B cells proliferate and hypermutate their immunoglobulin genes, and mutants with increased affinity are positively selected in the light zone (LZ) to either differentiate into plasma and memory cells, or re-enter the DZ for further refinement. However, the molecular circuits governing GC positive selection are not known. Here, we show that the GC reaction requires the biphasic regulation of c-MYC expression, involving its transient induction during early GC commitment, its repression by BCL6 in DZ B cells, and its re-induction in a subpopulation of positively selected LZ B cells destined to DZ re-entry. Accordingly, acute disruption of MYC function in vivo leads to GC collapse, indicating an essential role in GC physiology. These results have implications for our understanding of GC selection and the role of MYC deregulation in B cell lymphomas.
Publication Title
The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
Illumina HiSeq 2500
Description
We used RNA sequencing to characterize gene expression of Ly75+/+ B1-8hi and Ly75-/- B1-8hi B cells from the germinal center light zone (LZ) 12 h after forcing positive selection of the Ly75+/+ population with anti-DEC205-OVA. Overall design: We primed C57BL/6 hosts with OVA-alum i.p. and after 2 weeks we adoptively transferred a mixture of B1-8hi B cells in which 15% were Ly75+/+ CD45.1 (DECP) and 85% were Ly75-/- CD45.1/2 (DECN). We then immunized the animals with NP-OVA in the footpads and after 6 days we injected anti-DEC205-OVA. 12 h or 24 h after anti-DEC205-OVA injection we sorted B220+ CD38- CD95+ CD45.1+ CD45.2- CD83hi CXCR4lo (DECPLZ) and B220+ CD38- CD95+ CD45.1+ CD45.2+ CD83hi CXCR4lo (DECNLZ) cells for whole transcriptome analysis by mRNA sequencing.
Publication Title
Germinal Center Selection and Affinity Maturation Require Dynamic Regulation of mTORC1 Kinase.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Somatic mutations of the MLL2 methyltransferase gene represent a common genetic lesion in multiple cancer types. In diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) (collectively, over 70% of all lymphoma diagnoses), these mutations are highly recurrent and appear early during transformation, possibly in pre-malignant precursors. Here we show that FL- and DLBCL-associated MLL2 mutations impair its enzymatic activity and lead to diminished global H3K4 methylation in normal germinal-center (GC) B cells and DLBCL, consistent with the enrichment of MLL2 binding at enhancer and promoter regions marked by mono- and tri-methylation. Conditional deletion of Mll2 early during B cell development, but not after initiation of the GC reaction, leads to increased percentages and numbers of GC B cells, which feature a distinct transcriptional profile defined by the enrichment of cell-cycle regulatory and B-cell receptor signaling genes. Consistently, Mll2-deficient B cells exhibit proliferative advantage and accumulation in the S phase of the cell cycle, which is influenced by the number of cell divisions. While GC-specific loss of Mll2 was not sufficient to initiate malignant transformation, compound Mll2-deficient/BCL2-transgenic mice displayed an increased incidence of clonal lymphoproliferations resembling the features of human FL and DLBCL. These findings suggest that early MLL2 loss favors BCL2-induced lymphomagenesis by remodeling the epigenetic landscape of the cancer precursor cells. Eradication of MLL2-deficient cells may represent a rational therapeutic approach targeting early tumorigenic events.
Publication Title
Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis.
Sample Metadata Fields
Sex, Specimen part
View Samples
GSE71274- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression studies comparing IFNg+ Tregs versus IFNg- Tregs from human peripheral blood
Publication Title
AKT isoforms modulate Th1-like Treg generation and function in human autoimmune disease.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 16 Downloadable Samples
- IlluminaHiSeq2500
Description
The RNA-binding protein FUS is implicated in transcription, alternative splicing of neuronal genes and DNA repair. Mutations in FUS have been linked to human neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). We genetically disrupted fus in zebrafish (Danio rerio) using the CRISPR-Cas9 system. The fus knockout animals are fertile and did not show any distinctive phenotype. Mutation of fus induces mild changes in gene expression on the transcriptome and proteome level in the adult brain. We observed a significant influence of genetic background on gene expression and 3’UTR usage, which could mask the effects of loss of Fus. Unlike published fus morphants, maternal zygotic fus mutants do not show motoneuronal degeneration and exhibit normal locomotor activity. Overall design: We performed paired-end sequencing (100bp reads) of the polyA+ transcriptome from brains of five individuals with Fus-/- genotype and four with Fus wild type genotype. Note on RNA-Seq replicates: after performing first RNA sequencing on four replicates of Fus-/- and WT (labeled with the prefix "Sample_imb_ketting_2014_13_") we received a notice from Illumina stating a problem with the library preparation kit lot that was used to prepare the libraries. Due to that, we performed RNA sequencing a second time, using the same input RNA, except for the Fus knockout replicate #3, because there was not enough input RNA left. Instead, a different Fus knockout replicate (#1) was sequenced. However, we compared the mapped reads from sequencing run 1 and sequencing run 2 using plotCorrelaction from DeepTools, and the samples are highly correlated (at least 0.97 and 0.95, Spearman and Pearson correlation respectively). Therefore, we considered first ("Sample_imb_ketting_2014_13_") and second sequencing runs as technical replicates.
Publication Title
Characterization of genetic loss-of-function of Fus in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Current pipelines used to map genetrap insertion sites are based on inverse- or splinkerette-PCR methods, which despite their efficacy are prone to artifacts and do not provide information on the impact of the genetrap on the expression of the targeted gene. We developed a new method, which we named TrapSeq, for the mapping of genetrap insertions based on paired-end RNA sequencing. By recognizing chimeric mRNAs containing genetrap sequences spliced to an endogenous exon, our method identifies insertions that lead to productive trapping. Overall design: We conducted two independent screenings for sensitivity against 6-thioguanine (6TG) and an ATR inhibitor (ATRi). We applied our RNAseq-based pipeline (TrapSeq) to identify mutations that provide resistance to these reagents. Importantly, and besides its use for screenings, when applied to individual clones our method provides a fast and cost-effective way that not only identifies the insertion site of the genetrap but also reveals the impact of the insertion on the expression of the trapped gene. Please note that HAP1, haploid for all chromosomes, derives from near-haploid KBM7 parent line which was in turn obtained from a chronic myeloid leukemia patient in blast crisis phase (Carette et al. Nature 477:340-343, 2011).
Publication Title
Trap<sup>Seq</sup>: An RNA Sequencing-Based Pipeline for the Identification of Gene-Trap Insertions in Mammalian Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples