Filters
Technology
Platform
SRP071058
Mus musculus
48 Downloadable Samples
Illumina HiSeq 2500
Description
B cells provide humoral immunity by differentiating into antibody secreting plasma cells. Differentiation is dependent upon division and transcriptional changes, with commitment to B cell lineages associated with epigenetic changes. Analysis of early transcriptional and epigenetic events in B cell differentiation revealed that plasmablasts and plasma cells undergo dynamic changes in gene expression and a progressive DNA hypomethylation targeted to at least 10% of genes/loci. Of the differentially methylated loci, more than 99.7% were demethylated during differentiation and these clustered in cis-regulatory features such as enhancers and transcription factor binding sites. Changes in gene expression and DNA methylation coincided with each other at specific divisions during differentiation and inhibition of DNA methylation resulted in augmented plasma cell commitment in a division-dependent manner. These data identify a major epigenetic reprogramming event during early B cell differentiation coupled division and provide an approach to modulating humoral immune responses. Overall design: Splenic B cells (B220+ CD43-) from naïve C57/BL6J mice were labeled with CFSE or CTV and transferred into uMT mice and allowed to rest overnight prior to challenge with LPS. Three days post challenge adoptively transferred B cells representing distinct divisions were sorted out for molecular analysis. These divisions are labelled Div0, Div1, Div3, Div5, Div8- and Div8+. Division 8- refers to cells that divided at least 8 times but were CD138-, whereas Division 8+ refers to cells that divided at least 8 times but were CD138+. Cells were subjected to RNA-seq and Reduced Representation Bisulfite Sequencing.
Publication Title
Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
B cells provide humoral immunity by differentiating into antibody secreting plasma cells. Differentiation is dependent upon division and transcriptional changes, with commitment to B cell lineages associated with epigenetic changes. Analysis of early transcriptional and epigenetic events in B cell differentiation revealed that plasmablasts and plasma cells undergo dynamic changes in gene expression and a progressive DNA hypomethylation targeted to at least 10% of genes/loci. Of the differentially methylated loci, more than 99.7% were demethylated during differentiation and these clustered in cis-regulatory features such as enhancers and transcription factor binding sites. Changes in gene expression and DNA methylation coincided with each other at specific divisions during differentiation and inhibition of DNA methylation resulted in augmented plasma cell commitment in a division-dependent manner. These data identify a major epigenetic reprogramming event during early B cell differentiation coupled division and provide an approach to modulating humoral immune responses.
Publication Title
Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 45 Downloadable Samples
- Illumina HiSeq 2500
Description
To understand the role of Ezh2 in B cell differentiation B cells were stimulated ex vivo with LPS, Il2, and Il5 in the presence of DMSO or the selective Ezh2 inhibitor GSK343. Following 3 days culture, activated B cells and Plasmablasts were FACS isolated and RNA-seq was performed to identify the molecular effects of Ezh2 inhibition on B cell subsets during differentiation. Overall design: RNAseq on ex vivo differentiated B cell subsets treated with GSK343 or DMSO
Publication Title
Plasma cell differentiation is controlled by multiple cell division-coupled epigenetic programs.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip, Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide promoter analysis of the SOX4 transcriptional network in prostate cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
To understand the role of LSD1 in B cell differentiation, mice with B cell conditional deletion of LSD1 were intravenously inoculated with LPS. After 3 days, B220+GL7-CD138- naïve B cells and CD138+ plasmablasts were FACS-sorted from the spleens and RNA-seq was performed to identify LSD1-target regulated genes. Overall design: RNA-seq on control or LSD1-deficient murine naïve B cells or plasmablasts.
Publication Title
The Histone Demethylase LSD1 Regulates B Cell Proliferation and Plasmablast Differentiation.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
SOX4 is a critical developmental transcription factor in vertebrates and is required for precise differentiation and proliferation in multiple tissues. In addition, SOX4 is overexpressed in many human malignancies, but the precise role of SOX4 in cancer progression is not well understood. Here we have performed an expression profiling experiment of LNCaP cells either overexpressing SOX4 or GFP to identify SOX4 target genes.
Publication Title
Genome-wide promoter analysis of the SOX4 transcriptional network in prostate cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
SOX4 is a critical developmental transcription factor in vertebrates and is required for precise differentiation and proliferation in multiple tissues. In addition, SOX4 is overexpressed in many human malignancies, but the precise role of SOX4 in cancer progression is not well understood. Here we have either eliminated SOX4 using siRNA or overexpressed a SOX4 cDNA and compared the gene expression patterns against control GFP transfections to identify SOX4 target genes.
Publication Title
Genome-wide promoter analysis of the SOX4 transcriptional network in prostate cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Memory B cell responses are more rapid and of greater magnitude than are primary antibody responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of antibody recall responses. ZBTB32 is highly expressed by mouse and human memory B cells, but not by their nave counterparts. Zbtb32-/- mice mount normal primary antibody responses to T-dependent antigens. However, Zbtb32-/- memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses. Microarray analyses demonstrate that Zbtb32-/- secondary bone marrow plasma cells display elevated expression of genes that promote cell cycle progression and mitochondrial function relative to wild-type controls. BrdU labeling and adoptive transfer experiments confirm more rapid production and a cell-intrinsic survival advantage of Zbtb32-/- secondary plasma cells relative to wild-type counterparts. ZBTB32 is therefore a novel negative regulator of antibody recall responses.
Publication Title
ZBTB32 Restricts the Duration of Memory B Cell Recall Responses.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Memory B cell responses are more rapid and of greater magnitude than are primary antibody responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of antibody recall responses. ZBTB32 is highly expressed by mouse and human memory B cells, but not by their nave counterparts. Zbtb32-/- mice mount normal primary antibody responses to T-dependent antigens. However, Zbtb32-/- memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses. Microarray analyses demonstrate that Zbtb32-/- secondary bone marrow plasma cells display elevated expression of genes that promote cell cycle progression and mitochondrial function relative to wild-type controls. BrdU labeling and adoptive transfer experiments confirm more rapid production and a cell-intrinsic survival advantage of Zbtb32-/- secondary plasma cells relative to wild-type counterparts. ZBTB32 is therefore a novel negative regulator of antibody recall responses.
Publication Title
ZBTB32 Restricts the Duration of Memory B Cell Recall Responses.
Sample Metadata Fields
Specimen part
View Samples