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GSE11766
Mus musculus
48 Downloadable Samples
Description
Levels of C/EBP are low in myeloid blast crisis (BC) of chronic myelogenous leukemia (CML) and its expression in p210BCR/ABL-expressing hematopoietic cells induces granulocytic differentiation, inhibits proliferation and suppresses leukemogenesis. To assess the mechanisms involved in these effects, C/EBP targets were identified by microarray analyses. Upon C/EBP activation, expression of c-Myb and GATA-2 was repressed in 32D-BCR/ABL, K562 and CML-BC primary cells but only c-Myb levels decreased slightly in CD34+ normal progenitors. The role of these two genes for the biological effects of C/EBP was assessed by perturbing their expression in K562 cells. Expression of c-Myb blocked the proliferation inhibition and differentiation-inducing effects of C/EBP while c-Myb siRNA treatment enhanced C/EBP-mediated proliferation inhibition and induced changes in gene expression indicative of monocytic differentiation. GATA-2 expression suppressed the proliferation inhibitory effect of C/EBP but blocked in part the effect on differentiation; GATA-2 siRNA treatment had no effects on C/EBP induction of differentiation but inhibited proliferation of K562 cells, alone or upon C/EBP activation. In summary, the effects of C/EBP in p210BCR/ABL -expressing cells depend, in part, on transcriptional repression of c-Myb and GATA-2. Since perturbation of c-Myb and GATA-2 expression has non identical consequences for proliferation and differentiation of K562 cells, the effects of C/EBP appear to involve different transcription-regulated targets.
Publication Title
Transcriptional repression of c-Myb and GATA-2 is involved in the biologic effects of C/EBPalpha in p210BCR/ABL-expressing cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Analysis of HSCs from control and c-myc N-myc deficient long-term hematopoietic stem cells. HSCs lacking both c-myc and N-myc display increased apoptosis rates. Data provide insight into the molecular changes occuring upon complete loss of Myc activity, clarifying the resulting apoptotic mechanism and the role of Myc family proteins in HSCs and commited progenitors.
Publication Title
Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
Analysis of HSCs from control and c-myc N-myc deficient long-term hematopoietic stem cells. HSCs lacking both c-myc and N-myc display increased apoptosis rates. Data provide insight into the molecular changes occuring upon complete loss of Myc activity, clarifying the resulting apoptotic mechanism and the role of Myc family proteins in HSCs.
Publication Title
Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Scl/Tal1 confers hemogenic competence and prevents cardiomyogenesis in embryonic endothelium. Here we show that Scl both directly activates a broad gene regulatory network required for hematopoietic stem/progenitor cell (HS/PC) development, and represses transcriptional regulators required for cardiogenesis. Cardiac repression occurs during a short developmental window through Scl binding to distant cardiac enhancers that harbor H3K4me1 at this stage. Scl binding to hematopoietic regulators extends throughout HS/PC and erythroid development and spreads from distant enhancers to promoters. Surprisingly, Scl complex partners Gata 1 and 2 are dispensable for hematopoietic versus cardiac specification and Scl binding to the majority of its target genes. Nevertheless, Gata factors co-operate with Scl to activate selected transcription factors to facilitate HS/PC emergence from hemogenic endothelium. These results uncover a dual function for Scl in dictating hematopoietic versus cardiac fate choice and suggest a mechanism by which lineage-specific bHLH factors direct the divergence of competing fates.
Publication Title
Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
Description
We used microarrays to detail the global programme of gene expression underlying cardiac development by HDAC2 and identified distinct classes of up-regulated and down-regulated genes during this process.
Publication Title
Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
Description
The cancer-risk associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long non-coding RNA CCAT2 in the highly amplified 8q24.21 region has been implicated in cancer predisposition, though causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by downregulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel disease-specific RNA mutation (named DNA-to-RNA allelic imbalance, DRAI) at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.
Publication Title
Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA <i>CCAT2</i> induce myeloid malignancies via unique SNP-specific RNA mutations.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 13 Downloadable Samples
Description
Ikaros family DNA binding proteins are critical regulators of B cell development. To identify Ikaros-regulated genes in pre-B cells we performed gene expression studies at enhanced temporal resolution.
Publication Title
Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Metabolic reprogramming induces resistance to anti-NOTCH1 therapies in T cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples