OBF1, also known as Bob.1 or OCA-B, is a B lymphocyte-specific transcription factor which coactivates Oct1 and Oct2 on B cell specific promoters. So far, the function of OBF1 has been mainly identified in late stage B cell populations. The central defect of OBF1 deficient mice is a severely reduced immune response to T cell-dependent antigens and a lack of germinal center formation in the spleen. Relatively little is known about a potential function of OBF1 in developing B cells. Here we have generated transgenic mice overexpressing OBF1 in B cells under the control of the immunoglobulin heavy chain promoter and enhancer. Surprisingly, these mice have greatly reduced numbers of follicular B cells in the periphery and have a compromised immune response. Furthermore, B cell differentiation is impaired at an early stage in the bone marrow. A first block is observed during B cell commitment and a second differentiation block is seen at the large preB2 cell stage. The cells that succeed to escape the block and to differentiate into mature B cells have post-translationally downregulated the expression of transgene, indicating that expression of OBF1 beyond the normal level early in B cell development is deleterious. Indeed ID3, which is a negative regulator of B cell differentiation, is upregulated in the EPLM and preB cells of the transgenic mice. Furthermore ID3 promoter contains an octamer site suggesting that it is a potential OBF-1 direct target gene. These results provide evidence that OBF1 expression has to be tightly regulated in early B cells to allow efficient B lymphocyte differentiation.
Enforced expression of the transcriptional coactivator OBF1 impairs B cell differentiation at the earliest stage of development.
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View SamplesUsing a stromal cell free system, we described the gene expression and two genome wide epigenetic profiles of a unique population of undifferentiated bone marrow cells selectively driven towards the T cell differentiation pathway
An epigenetic profile of early T-cell development from multipotent progenitors to committed T-cell descendants.
Specimen part, Treatment
View SamplesThalidomide Exerts Distinct Molecular Antileukemic Effects and Combined Thalidomide/Fludarabine Therapy is Clinically Effective in High-Risk Chronic Lymphocytic Leukemia
Thalidomide exerts distinct molecular antileukemic effects and combined thalidomide/fludarabine therapy is clinically effective in high-risk chronic lymphocytic leukemia.
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View SamplesWe performed a single-cell transcriptome analysis of double-negative developing thymocytes from the DN2, DN3 and DN4 populations Overall design: Double-negative developing thymocytes from the DN2, DN3 and DN4 populations were sorted from six WT mice and used for single cell RNA Seq (10x genomics platform)
The transcription factor Duxbl mediates elimination of pre-T cells that fail β-selection.
Sex, Specimen part, Cell line, Subject
View SamplesWe performed a transcriptome comparison of double-negative developing thymocytes from the DN3-4 population, from mice overexpressing the transcription factor Duxbl and wild type mice Overall design: Double-negative developing thymocytes from both WT and Duxbl[ind]xpTa[Cre] mice were gated for CD4-, CD8-, CD3-, B220-, CD25int, CD44low and CD117low expression, which define the DN3-4 stage of thymocyte development. The experiment was performed in four replicates, giving a total of 8 samples.
The transcription factor Duxbl mediates elimination of pre-T cells that fail β-selection.
Sex, Cell line, Subject
View SamplesTwo major subsets of rat natural killer (NK) cells can be distinguished based on their expression of either the Ly49s3 or the NKR-P1B lectin-like receptor. Ly49s3+ NK cells, but not NKR-P1B+ NK cells, express a wide range of Ly49 receptors.
Two complementary rat NK cell subsets, Ly49s3+ and NKR-P1B+, differ in phenotypic characteristics and responsiveness to cytokines.
Specimen part
View SamplesThe Fulani ethnic group is relatively protected from Plasmodium falciparum malaria, however a genetic basis for this is unknown. Therefore, we have performed a pilot study to examine global transcription and DNA methylation patterns in specific immune cell populations in the Fulani, compared to a sympatric ethnic group, the Mossi. When we compared uninfected and infected individuals in Fulani and Mossi, a strong transcriptional response was only detected in the monocyte fraction of Fulani, and this was not related to differences in DNA methylation. Overall design: RNA sequencing analysis of CD14+ (monocyte) and CD14- (predominantly lymphocyte), and DNA-methylation analysis of CD14+ (monocyte) fractions of PBMCs, from of Fulani and Mossi individuals, uninfected or infected with P.falciparum. This Series represents the RNA-Seq dataset.
Major transcriptional changes observed in the Fulani, an ethnic group less susceptible to malaria.
Subject
View SamplesDiabetes and obesity are widespread diseases with signifciant socioeconomic implications. We used three different types of human adipose tissue (epigastric, visceral, and subcutaneous) in order to determine differences in global gene expression between these adipose depots in severely obese patients.
Gene expression profiling in subcutaneous, visceral and epigastric adipose tissues of patients with extreme obesity.
Specimen part, Race
View SamplesOxidative DNA damage has been associated with cognitive decline. The Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic oxidative DNA base lesion. Here, we have examined behavior and cognitive function in mice deficient of these glycosylases. We found that Ogg1-/-Mutyh-/- mice were more active and less anxious and that their learning ability was impaired. In contrast, Mutyh-/- mice showed moderately improved memory compared to WT. There was no change in genomic 8-oxoG levels, suggesting that Ogg1 and Mutyh play minor roles in global repair in adult brain. Notably, transcriptome analysis of hippocampus revealed that differentially expressed genes in the mutant mice belong to pathways known to be involved in anxiety and cognitive function. Thus, beyond their involvement in DNA repair, Ogg1 and Mutyh modulate cognitive function and behavior, and related hippocampal gene expression, suggesting a novel role for 8-oxoG in regulating adaptive behavior. Overall design: The mRNA profiles from hippocampus of WT, Ogg1-/-, Mutyh-/- and Ogg1-/- Mutyh-/- C57BL/6 mice at 6month of age were generated by RNA sequencing using Illumina Hiseq 2000
Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice.
Age, Specimen part, Cell line, Subject
View SamplesSWP73 subunits of SWI/SNF chromatin remodeling complexes (CRCs) are involved in key developmental pathways in Arabidopsis. We found, using microarray that inactivation of SWP73B caused altered expression of genes belonging to various regulatory pathways, including leaf and flower development. On the basis of this experiment and our other data we concluded that SWP73B modulates major developmental pathways.
SWP73 Subunits of Arabidopsis SWI/SNF Chromatin Remodeling Complexes Play Distinct Roles in Leaf and Flower Development.
Specimen part
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