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SRP047323
Homo sapiens
18 Downloadable Samples
IlluminaHiSeq2500, IlluminaHiSeq2000
Description
Burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) cells are erythroid progenitors traditionally defined by colony assays. We developed a flow cytometry-based strategy for isolating human BFU-E and CFU-E cells based on the changes in expression of cell surface markers during in vitro erythroid cell culture. BFU-E and CFU-E are characterized by CD45+GPA-IL-3R-CD34+CD36-CD71low and CD45+GPA-IL-3R-CD34-CD36+CD71high phenotypes, respectively. Colony assays validated phenotypic assignment giving rise to BFU-E and CFU-E colonies, both at a purity ~90%. The BFU-E colony forming ability of CD45+GPA-IL-3R-CD34+CD36-CD71low cells required SCF and erythropoietin, while the CFU-E colony forming ability of CD45+GPA-IL-3R-CD34-CD36+CD71high cells required only erythropoietin. Bioinformatic analysis of the RNA-seq data revealed unique transcriptomes in each differentiation stage. The sorting strategy was validated in uncultured primary cells isolated from bone marrow and peripheral blood, indicating that marker expression is not an artifact of in vitro cell culture, but represents an in vivo characteristic of erythroid progenitor populations. The ability to isolate highly pure human BFU-E and CFU-E progenitors will enable detailed cellular and molecular characterization of these distinct progenitor populations and define their contribution to disordered erythropoiesis in inherited and acquired hematological disease. Our data provide important resource for future studies. Overall design: Transcription profiles of Human erythroid progenitors at distinct developmental stages were generated by deep sequencing, in triplicate, using IlluminaHiSeq 2000. The complete dataset comprises 4 sample types: CD34, BFU, CFU, and Pro (reanalysis of GSM1304777-GSM1304779).
Publication Title
Isolation and transcriptome analyses of human erythroid progenitors: BFU-E and CFU-E.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
RNAseq analysis of BAFF in vitro-stimulated (6 hours) murine nfkb2fl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor NF-kB2 in BAFF-stimulated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with BAFF. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Publication Title
Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-κB Transcription Factors RELB and NF-κB2 in B Cells.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
RNAseq analysis of CD40 in vitro-stimulated (6 hours) murine nfkb2fl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor NF-kB2 in activated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Publication Title
Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-κB Transcription Factors RELB and NF-κB2 in B Cells.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 32 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Macrophage polarization between the M2 (repair, pro-tumorigenic) and M1 (inflammatory) phenotypes is seen as a continuum of states. The detailed transcriptional events and signals downstream of CSF-1R that contribute to amplification of the M2 phenotype and suppression of the M1 phenotype are largely unknown. Macrophage CSF-1R pTyr-721 signaling promotes cell motility and enhancement of tumor cell invasion in vitro. Combining analysis of cellular systems for CSF-1R gain-of-function and loss-of-function with bioinformatic analysis of the macrophage CSF-1R pTyr-721-regulated transcriptome, we uncovered miR-21 as a downstream molecular switch controlling macrophage activation and identified ERK1/2 and NF-B as CSF-1R pTyr-721-regulated signaling nodes. We show that CSF-1R pTyr-721 signaling suppresses the proinflammatory phenotype, predominantly by induction of miR-21. Profiling of the miR-21-regulated mRNAs revealed that 80% of the CSF-1-regulated canonical miR-21 targets are pro-inflammatory molecules. Additionally, miR-21 positively regulates M2 marker expression. Moreover, miR-21 feeds back to positively regulate its own expression and to limit CSF-1R-mediated activation of ERK1/2 and NF-B. Consistent with an anti-inflammatory role of miRNA-21, intraperitoneal injection of mice with a miRNA-21 inhibitor increases the recruitment of inflammatory monocytes and enhances the peritoneal monocyte/macrophage response to lipopolysaccharide (LPS).
Publication Title
Colony stimulating factor-1 receptor signaling networks inhibit mouse macrophage inflammatory responses by induction of microRNA-21.
Alternate Accession IDs
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The adaptor protein LNK (SH2B3) has emerged as an important protein in regulating B cell development B cell leukemia. Loss-of-function mutations in LNK (SH2B3) are found in Philadelphia chromosomelike acute lymphoblastic leukemia (Ph-like ALL), but how LNK regulates normal B cell development or promotes leukemogenesis remains unclear. We found that combined loss of Lnk and tumor suppressors Tp53 in mice triggers a highly aggressive and transplantable precursor B-ALL. This study aims to investigate the molecular mechanism by which LNK regulates B-ALL development. We performed expression profiling of bone marrow proB progenitors from WT, Tp53-/-, Lnk-/- and preleukemic healthy Tp53/Lnk double knockout (DKO) mice, as well as leukemic bone marrow cells from DKO mice that have developed B-ALL. Results suggest that Tp53-/-Lnk-/- B-ALLs display similar gene expression profiles to human Ph-like B-ALLs, suggesting this model for preclinical and molecular studies.
Publication Title
LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA-seq analysis of murine eGFP+ relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre splenic germinal center B cells identifies genes regulated by the transcription factors RELB and p52 (NF-kB2) in germinal center B cells. Overall design: Germinal center B cells from 12-week old relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre littermate mice immunized with sheep red blood cells (SRBC) were isolated at day 7 after immunization by flow cytometric sorting from splenic mononuclear cells. RNA was isolated, amplified and submitted for RNA-sequencing on an Illumina HiSeq2500 instrument for 35-40 million 2x50 paired-ended reads.
Publication Title
Transcription factors of the alternative NF-κB pathway are required for germinal center B-cell development.
Alternate Accession IDs
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Genome occupancy profiling by high throughput sequencing Overall design: PolyA selected RNA-seq for shRNA-expressing MLL-AF9 transformed acute myeloid leukemia cells (RN2)
Publication Title
BET Bromodomain Inhibition Releases the Mediator Complex from Select cis-Regulatory Elements.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 1 Downloadable Sample
- NextSeq 500
Description
Gjd3-CreEGFP mice is a novel genetic tool to study the structural and molecular signatures of Atrioventricular Node (AVN) at a high resolution. Overall design: Focusing on the cardiac conduction system, we developed and rigorously characterized a geentic tool Gjd3-CreEGFP to perform in-depth analysis of AVN structure and composition. Utilizing this AVN-specific mouse model, we performed scRNA-Seq on neonatal Gjd3-CreEGFP mice to guide our single-cell atlas of the Atrio-ventricular conduction system (AVCS).
Publication Title
Using Gjd3-CreEGFP mice to examine atrioventricular node morphology and composition.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL). We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL). To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM) model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (E). Here, we report that the E-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD) with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of E-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors.
Publication Title
Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples