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SRP042164
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
The proliferation and survival of hematopoietic stem cells (HSCs) has to be strictly coordinated to ensure the timely production of all blood cells. Here we report that the splice factor and RNA binding protein hnRNP L (heterogeneous nuclear ribonucleoprotein L) is required for hematopoiesis, since its genetic ablation in mice reduces almost all blood cell lineages and causes premature death of the animals. In agreement with this, we observed that hnRNP L deficient HSCs lack both the ability to self-renew and foster hematopoietic differentiation in transplanted hosts. They also display mitochondrial dysfunction, elevated levels of ?H2AX, are Annexin V positive and incorporate propidium iodide indicating that they undergo cell death. Lin(-)c-Kit(+) fetal liver cells from hnRNP L deficient mice show high p53 protein levels and up-regulation of p53 target genes. In addition, cells lacking hnRNP L up-regulated the expression of the death receptors TrailR2 and CD95/Fas and show Caspase-3, Caspase-8 and Parp cleavage. Treatment with the pan-caspase inhibitor Z-VAD-fmk, but not the deletion of p53, restored cell survival in hnRNP L deficient cells. Our data suggest that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways. Overall design: fetal liver cells from either hnRNPL wild-type or hnRNPL KO embryos were analysed for differential expression and alternative splicing by RNA-Seq. RNA-Seq was carried out in biological triplicate for each sample type. Each sample is a single embryo.
Publication Title
Heterogeneous Nuclear Ribonucleoprotein L is required for the survival and functional integrity of murine hematopoietic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Quiescent and dividing hemopoietic stem cells (HSC) display marked differences in their ability to move between the peripheral circulation and the bone marrow. Specifically, long-term engraftment potential predominantly resides in the quiescent HSC subfraction, and G-CSF mobilization results in the preferential accumulation of quiescent HSC in the periphery. In contrast, stem cells from chronic myeloid leukemia (CML) patients display a constitutive presence in the circulation. To understand the molecular basis for this, we have used microarray technology to analyze the transcriptional differences between dividing and quiescent, normal, and CML-derived CD34+ cells.
Publication Title
Transcriptional analysis of quiescent and proliferating CD34+ human hemopoietic cells from normal and chronic myeloid leukemia sources.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ptf1a was identified as the essential transcription factor which controls pancreatic exocrine enzyme expression. With lineage tracing eperiments Ptf1a was recognized as an important pancreatic progenitor transcription factor and Ptf1a null mice do not develop a pancreas.
Publication Title
RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Genes specific to Sox9+ pancreatic progenitors were identified by comparing the gene expression in embryonic and adult Sox9+ cells.
Publication Title
A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Microarray studies revealed that as a first hit, SV40 T/t-antigen causes deregulation of 462 genes in mammary gland cells (ME-cells) of WAP-SVT/t transgenic animals. The majority of deregulated genes are cell-proliferation specific and Rb-E2F dependent, causing ME-cell proliferation and gland hyperplasia but not breast cancer formation. In the breast tumor cells, a further 207 genes are differentially expressed, most of them belonging to the cell communication category. In tissue culture, breast tumor cells frequently switch off WAP-SVT/t transgene expression and regain the morphology and growth characteristics of normal-ME-cells, although the tumor-revertant cells are aneuploid and only 114 genes regain the expression level of normal-ME-cells. The profile of retransformants shows that only 38 deregulated genes appear to be tumor-relevant and that none of them is considered to be a typical breast cancer gene.
Publication Title
Gene expression profiling: cell cycle deregulation and aneuploidy do not cause breast cancer formation in WAP-SVT/t transgenic animals.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Alternative promoters (APs) occur in >30% protein-coding genes and contribute to proteome diversity. However, large-scale analyses of AP regulation are lacking, and little is known about their potential physiopathologic significance. To better understand the transcriptomic impact of estrogens, which play a major role in breast cancer, we analyzed gene and AP regulation by estradiol in MCF7 cells using pan-genomic exon arrays. We thereby identified novel estrogen-regulated genes, and determined the regulation of AP-encoded transcripts in 150 regulated genes. In <30% cases, APs were regulated in a similar manner by estradiol, while in >70% cases, they were regulated differentially. The patterns of AP regulation correlated with the patterns of estrogen receptor (ER) and CCCTC-binding factor (CTCF) binding sites at regulated gene loci. Interestingly, among genes with differentially regulated APs, we identified cases where estradiol regulated APs in an opposite manner, sometimes without affecting global gene expression levels. This promoter switch was mediated by the DDX5/DDX17 family of ER coregulators. Finally, genes with differentially regulated promoters were preferentially involved in specific processes (e.g., cell structure and motility, and cell cycle). We show in particular that isoforms encoded by the NET1 gene APs, which are inversely regulated by estradiol, play distinct roles in cell adhesion and cell cycle regulation, and that their expression is differentially associated with prognosis in ER+ breast cancer. Altogether, this study identifies the patterns of AP regulation in estrogen-regulated genes, demonstrates the contribution of AP-encoded isoforms to the estradiol-regulated transcriptome, as well as their physiopathologic significance in breast cancer.
Publication Title
Estrogen regulation and physiopathologic significance of alternative promoters in breast cancer.
Sample Metadata Fields
Disease, Disease stage, Cell line, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This study was designed to compare the global gene expression change induced by the circulating, prodomain bound forms of BMP9 and BMP10 (pro-BMP9 and pro-BMP10) in human pulmonary arterial endothelial cells (PAECs). This is different from many previous studies which used the growth factor domain of BMP9 and/or BMP10.
Publication Title
Molecular basis of ALK1-mediated signalling by BMP9/BMP10 and their prodomain-bound forms.
Sample Metadata Fields
Sex, Age
View Samples- Glycine max
- 11 Downloadable Samples
- Affymetrix Soybean Genome Array (soybean)
Description
This study was designed to identify candidate genes associated with iron efficiency in soybeans. Two genotypes, Clark (PI548553) and IsoClark (PI547430), were grown in both iron sufficient (100uM Fe(NO3)3) and iron deficient (50uM Fe(NO3)3) hydroponics conditions. The second trifoliate was harvested for RNA extraction for the microarray experiment. Candidate genes were identified by comparing gene expression profiles within genotypes between the two iron growth conditions.
Publication Title
Integrating microarray analysis and the soybean genome to understand the soybeans iron deficiency response.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Adenovirus infection leads to increased glycolytic metabolism in host cells. Expression of a single gene product encoded within the E4 early transcription region, E4ORF1, is sufficient to promote increased glycolytic flux in cultured epithelial cells.
Publication Title
Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Microarrays were used to detail the global programme of gene expression comparing wild-type and RNAi knock-down plants of SPT4-1 and SPT4-2
Publication Title
The transcript elongation factor SPT4/SPT5 is involved in auxin-related gene expression in Arabidopsis.
Sample Metadata Fields
Age, Specimen part
View Samples