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GSE43401
Homo sapiens
43 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A dosage-dependent role for tumor suppressor genes in the initiation of myeloid malignancies remains controversial. Here we show that MYBL2 is expressed at sharply reduced levels in CD34+ cells from most patients with myelodysplastic syndrome (MDS; 65%; n=26). In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors led to clonal dominance by these sub-haploinsufficient cells, affecting all blood cell lineages. By 6 months post-transplantation, the reconstituted mice had developed a myeloproliferative/myelodysplastic disorder originating from the cells with aberrantly reduced Mybl2 expression. Thus, downregulation of MYBL2 activity to levels below those predicted by classical haploinsufficiency drives the clonal expansion of hematopoietic progenitors in a large fraction of human MDS cases.
Publication Title
MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A dosage-dependent role for tumor suppressor genes in the initiation of myeloid malignancies remains controversial. Here we show that MYBL2 is expressed at sharply reduced levels in CD34+ cells from most patients with myelodysplastic syndrome (MDS; 65%; n=26). In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors led to clonal dominance by these sub-haploinsufficient cells, affecting all blood cell lineages. By 6 months post-transplantation, the reconstituted mice had developed a myeloproliferative/myelodysplastic disorder originating from the cells with aberrantly reduced Mybl2 expression. Thus, downregulation of MYBL2 activity to levels below those predicted by classical haploinsufficiency drives the clonal expansion of hematopoietic progenitors in a large fraction of human MDS cases.
Publication Title
MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
mRNA from bone marrow-derived MSCs stably expressing CTGF-specific shRNA (or empty vector control) was analyzed for differential gene expression. Significant differences were found in cell proliferation-related genes, especially genes related to the M phase of the cell cycle, which were down-regulated in CTGF-knockdown-MSCs compared to control MSCs.
Publication Title
Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Telomere dysfunction drives aberrant hematopoietic differentiation and myelodysplastic syndrome.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Telomere dysfunctional CMP/GMP have deregulated pathways that are associated with DNA damage signaling
Publication Title
Telomere dysfunction drives aberrant hematopoietic differentiation and myelodysplastic syndrome.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
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- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Using high throughput sequencing of Drosophila head RNA, a small set of miRNAs that undergo robust circadian oscillations in levels were discovered. We concentrated on a cluster of six miRNAs, mir-959-964, all of which peak at about ZT12 or lights-off. The data indicate that the cluster pri-miRNA is transcribed under bona fide circadian transcriptional control and that all 6 mature miRNAs have short half-lives, a requirement for oscillating. Manipulation of food intake dramatically affects the levels and timing of cluster miRNA transcription with no more than minor effects on the core circadian oscillator. This indicates that the central clock regulates feeding, which in turn regulates proper levels and cycling of the cluster miRNAs. Viable Gal4 knock-in as well as cluster knock-out and over-expression strains were used to localize cluster miRNA expression as well as explore their functions. The adult head fat body is a major site of expression, and feeding behavior, innate immunity, metabolism, and perhaps stress responses are under cluster miRNA regulation. The feeding behavior results indicate that there is a feedback circuit between feeding time and cluster miRNA function as well as a surprising role of post-transcriptional regulation in these behaviors and physiology.
Publication Title
The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
Illumina Genome Analyzer II
Description
Using high throughput sequencing of Drosophila head RNA, a small set of miRNAs that undergo robust circadian oscillations in levels were discovered. We concentrated on a cluster of six miRNAs, mir-959-964, all of which peak at about ZT12 or lights-off. The data indicate that the cluster pri-miRNA is transcribed under bona fide circadian transcriptional control and that all 6 mature miRNAs have short half-lives, a requirement for oscillating. Manipulation of food intake dramatically affects the levels and timing of cluster miRNA transcription with no more than minor effects on the core circadian oscillator. This indicates that the central clock regulates feeding, which in turn regulates proper levels and cycling of the cluster miRNAs. Viable Gal4 knock-in as well as cluster knock-out and over-expression strains were used to localize cluster miRNA expression as well as explore their functions. The adult head fat body is a major site of expression, and feeding behavior, innate immunity, metabolism, and perhaps stress responses are under cluster miRNA regulation. The feeding behavior results indicate that there is a feedback circuit between feeding time and cluster miRNA function as well as a surprising role of post-transcriptional regulation in these behaviors and physiology. Overall design: Six samples of small RNA libraries (RNA size 19 to 29 nucleotides long) were prepared from Drosophila heads, each collected at one circadian time point during a light-dark cycle (ZT0, ZT4, ZT8, ZT12, ZT16, ZT20).
Publication Title
The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples