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SRP150686
Mus musculus
94 Downloadable Samples
Illumina HiSeq 2500
Description
Delineating key HSC regulators is of significant interest for informing the treatment of hematologic malignancy. While HSC activity is enhanced by overexpression of SKI, the transforming growth factor-beta (TGFß) signaling antagonist corepressor, its requirement in HSC is unknown. Here we reveal a profound defect in Ski-/- HSC fitness but not specification. Transcriptionally, Ski-/- HSC exhibited striking upregulation of TGFb superfamily signaling and splicing alterations. As these are both common aspects of myelodysplastic-syndrome (MDS) pathobiology with prognostic value, we investigated the role of SKI in MDS. A SKI-correlated gene signature defines a subset of low-risk MDS patients with active TGFß signaling and deregulated RNA splicing (e.g. CSF3R). The apparent paradox of Ski-/- HSC sharing molecular aspects of MDS with elevated SKI-mRNA is resolved by miR-21 targeting of SKI in MDS. We conclude that miR-21-mediated loss of SKI contributes to early stage MDS pathogenesis by activating TGFß signaling and alternative splicing while hindering HSC fitness. Overall design: Single cell RNA seq of transplanted fetal liver-derived hematopoietic stem cells
Publication Title
<i>SKI</i> controls MDS-associated chronic TGF-β signaling, aberrant splicing, and stem cell fitness.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
MLL-rearranged acute myeloid leukemia (AML) remains a fatal disease with a high rate of relapse and therapeutic failure due to chemotherapy resistance. In analysis of our Affymetrix microarray profiling of human AML and normal control samples, we found that ALOX5 is especially down-regulated in MLL-rearranged AML. Our colony forming/replating and bone marrow transplantation (BMT) assays showed that Alox5 exhibited a moderate anti-tumor effect both in vitro and in vivo. Strikingly, leukemic cells with Alox5 overexpression showed a significantly higher sensitivity to the standard chemotherapeutic agents, i.e., doxorubicin (DOX) and cytarabine (Ara-C). The drug-sensitizing role of Alox5 was further confirmed in human and murine MLL-rearranged AML cell models in vitro, as well as in the in vivo MLL-rearranged AML BMT model coupled with treatment of “5+3” (i.e. DOX plus Ara-C) regimen. Our RNA-seq analysis showed that Stat and K-Ras signaling pathways were negatively correlated with Alox5 overexpression in MLL-AF9-leukemic blast cells, implying targeting those pathways likely contributes to Alox5's functions. Collectively, our work shows that ALOX5 plays a moderate anti-tumor role and functions as a drug sensitizer, with a therapeutic potential, in MLL-rearranged AML. Overall design: To delineate the potential molecular mechanism underlying the anti-tumor and drug-sensitizing effects of Alox5, we performed RNA sequencing (RNA-seq) of two pairs (4 samples) of mouse BM leukemic blast cells collected from the MA9_Ctrl and MA9_Alox5 mice in secondary BMT assays.
Publication Title
ALOX5 exhibits anti-tumor and drug-sensitizing effects in MLL-rearranged leukemia.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 1000
Description
To evaluate the effect of IGF2BPs on mRNA stability and gene expression output, we conducted RNA-seq in individual IGF2BP knockdown and control HepG2 cells with or without actinomycin D treatment. Our RNA-seq and RNA stability profiling revealed that IGF2BPs were involved in RNA stability regulation and contributed to the stabilization of the transcriptome. Overall design: HepG2 cells were infected with individual lentiviral IGF2BP shRNA and non-specific control (shNS), and selected by puromycin to generate stable knockdown lines. We treated HepG2 cells with actinomycin D to inhibit transcription and collected cells at indicated time points (i.e., 0h, 1h, 3h, 6h). The total RNA was extracted by miRNeasy Kit (Qiagen) and sequenced by Illumina. For IGF2BP-dependent gene expression, untreated cells (i.e., 0h samples) were sequenced in triplicate and analyzed. For RNA stability profiling, RNA half-life was calculated by comparing the gene expression at 1, 3, 6 hours with actinomycin treatment to that in un-treated samples, with two biological replicates for each group.
Publication Title
Recognition of RNA N<sup>6</sup>-methyladenosine by IGF2BP proteins enhances mRNA stability and translation.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA-seq from R-2HG sensitive leukemia cells treated with R-2HG or PBS. Overall design: With MTT assays, we identified R-2HG exhibits an anti-leukemia function. We conducted RNA-Seq in the two sensitive cells (NOMO-1 and MA9.3ITD) with R-2HG or without R-2HG treatment for 48 hours to investigate which genes/a-ketoglutarate-dependent dioxygenases/signaling pathways are responsible for the anti-leukemia function of R-2HG. For each group, there are three duplicates.
Publication Title
R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m<sup>6</sup>A/MYC/CEBPA Signaling.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide DNA methylation analysis of articular chondrocytes reveals a cluster of osteoarthritic patients.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 19 Downloadable Samples
- Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The aim of this study is to identify, for the first time, the genome-wide DNA methylation profiles of human articular chondrocytes from OA and healtly cartilage samples.
Publication Title
Genome-wide DNA methylation analysis of articular chondrocytes reveals a cluster of osteoarthritic patients.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Sus scrofa
- 12 Downloadable Samples
Affymetrix Porcine Genome Array (porcine)
Description
Previous results from a genome scan in a F2 Iberian by Meishan intercross showed several chromosome regions associated with litter size traits. In order to identify candidate genes underlying these QTL we have performed an ovary gene expression analysis during pregnancy. F2 sows were ranked by their estimated breeding values for prolificacy, the six sows with higher EBV (HIGH prolificacy) and the six with lower EBV (LOW prolificacy) were selected. Samples were hybridized to Affymetrix porcine expression microarrays. The statistical analysis with a mixed-model approach identified 221 differentially expressed probes, representing 189 genes. These genes were functionally annotated in order to identify the genetic pathways overrepresented. Among the most represented functional groups the first one was immune system response activation against external stimulus. The second group was made up of genes which regulate the maternal homeostasis by complement and coagulation cascades. The last group was involved on lipid and fatty acid enzymes of metabolic processes, which participate in steroidogenesis pathway. In order to identify powerful candidate genes for prolificacy, the second approach of this study was merging microarray data with position information of QTL affecting litter size, previously detected in the same experimental cross. According to this, we have identified 27 differentially expressed genes co-localized with QTL for litter size traits, which fulfill the biological, positional and functional criteria.
Publication Title
Differential gene expression in ovaries of pregnant pigs with high and low prolificacy levels and identification of candidate genes for litter size.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 63 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Artificial selection has resulted in animal breeds with extreme phenotypes. As an organism is made up of many different tissues and organs, each with its own genetic programme, it is pertinent to ask what are the relative contributions of breed or sex when assessed across tissues.
Publication Title
Transcriptome architecture across tissues in the pig.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Publication Title
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where pluripotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. The genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.
Publication Title
Motif discovery in promoters of genes co-localized and co-expressed during myeloid cells differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples