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GSE14365
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Aire is an important transcription regulator that mediates a role in central tolerance via promoting the promiscuous expression of tissue-specific antigens in the thymus. Although several mouse models of Aire-deficiency have been described, none has analysed the phenotype induced by a mutation that emulates the common 13bp deletion in human APECED by disrupting the first PHD domain in exon 8. Aire-deficient mice with a corresponding mutation showed some disturbance of the medullary epithelial compartment, but at the phenotypic level their T cell compartment appeared relatively normal in the thymus and periphery. An increase in the number of activated T cells was evident, and autoantibodies against several organs were detected. At the histological level, lymphocytic infiltration of several organs indicated the development of autoimmunity, though symptoms were mild and quality of life for Aire-deficient mice appeared equivalent to wild-type littermates, with the exception of male infertility. Vbeta and CDR3 length analysis suggested that each Aire-deficient mouse developed it own polyclonal autoimmune repertoire. Finally, given the prevalence of candidiasis in APECED patients, we examined the control of infection with Candida albicans in Aire-deficient mice. No increase in disease susceptibility was found for either oral or systematic infection. These observations support the view that additional genetic and/or environmental factors contribute substantially to the overt nature of autoimmunity associated with Aire mutations, even for mutations identical to those found in humans with APECED.
Publication Title
Aire-deficient C57BL/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Zea mays
- 29 Downloadable Samples
Illumina HiSeq 2000
Description
Plants have developed complex mechanisms to respond and adapt to abiotic stresses, coupling elaborate modulation of gene expression together with the preservation of genome stability. Epigenetic mechanisms - DNA methylation, chromatin modifications and non coding RNAs - were shown to play a fundamental role in stress-induced gene regulation and may also result in genome destabilization, with the activation and/or the transcription of silenced transposons and retroelements, causing genome rearrangements and novel gene expression patterns. Maize leaf transcriptome was analyzed by total RNA-Seq in both B73 and rmr6 (PolIV mutant involved in siRNA biogenesis and in the RdDM pathway) after drought and salt stress application. Reference annotation based transcript assembly allowed the identification both of new expressed loci and splicing variants, improving the current maize transcriptome annotation. Many antisense transcripts matching on the opposite strand of annotated loci were also identified, while more than the 20% of transcripts represent non coding RNA belonging to four classes: siRNAs, shRNAs, lncRNAs and transposable elements (or their relics). Several lncRNAs are modulated by stress application while TE-related sequences are mainly expressed in rmr6 and up-regulated by the stress. Overall design: Total RNA-Seq analysis of maize leaves from wt and rmr6-1 mutant plants grown under 1) control conditions, 2) drought stress, 3) salt stress, 4) salt+drought stress. Each condition was investigated in triplicate after 10 days of treatment and after 7 days of recovery. Samples derived from replicates 2 and 3 were pooled and sequenced together
Publication Title
Maize RNA PolIV affects the expression of genes with nearby TE insertions and has a genome-wide repressive impact on transcription.
Sample Metadata Fields
Treatment, Subject, Time
View Samples- Zea mays
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Histone deacetylases (HDACs) catalyze the removal of acetyl groups from acetylated histone tails that consequently interact more closely with DNA, leading to chromatin state refractory to transcription. Zea mays HDA108 belongs to the Rpd3/HDA1 HDAC family and is ubiquitously expressed during development. The newly isolated hda108/hda108 insertional mutant exhibited many developmental defects: significant reduction in plant height, alterations of shoot and leaf development, alterations of inflorescence patterning and fertility. Western blot analyses and immunolocalization experiments revealed an evident increase in histone acetylation, accompanied by a marked reduction in H3K9 dimethylation, in mutant nuclei. The DNA methylation status, in the CHG sequence context, and the transcript level of ribosomal sequences were also affected in hda108 mutants, while enrichment in H3 and H4 acetylation characterizes both repetitive and non-repetitive transcriptional up-regulated loci. RNA-Seq both of young leaf and anthers indicated that transcription factor expression is highly affected and that the pollen developmental programme results as disrupted in hda108 mutants. Crosses between hda108/hda108 and epiregulator mutants did not produce any double mutant progeny indicating possible genetic interactions of HDA108 with distinct epigenetic pathways. Our findings indicate that HDA108 is directly involved in regulation of maize development, fertility and epigenetic regulation of genome activity. Overall design: Total RNA-Seq analysis of maize anthers at post-meiotic (PMeA) and mitotic (MiA) stages. 2 biological replicates for stage, each obtained by pooling anthers from three tassels per genotype were collected from wild-type and hda108 mutant plants. Strand-specific sequencing on a Illumina HiSeq2500
Publication Title
Control of Maize Vegetative and Reproductive Development, Fertility, and rRNAs Silencing by <i>HISTONE DEACETYLASE 108</i>.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Digital gene expression profiling of primary acute lymphoblastic leukemia cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of this study was to benchmark digital gene expression (DGE) profiling by massively parallel sequencing against the most commonly used method for gene expression analysis. We compared the DGE levels to expression levels from Affymetrix arrays. Data from Affymetrix Human Genome U133 plus 2.0 GeneChips was available for 12 of the 21 RNA samples from ALL patient cells analyzed by DGE.
Publication Title
Digital gene expression profiling of primary acute lymphoblastic leukemia cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 83 Downloadable Samples
- IlluminaHiSeq2000
Description
Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: study of transcriptome during the development of MLL-AF9 AML
Publication Title
Modeling human MLL-AF9 translocated acute myeloid leukemia from single donors reveals RET as a potential therapeutic target.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 63 Downloadable Samples
- IlluminaHiSeq2000
Description
Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: study of transcriptome during the development of MLL-AF9 B-ALL
Publication Title
Modeling human MLL-AF9 translocated acute myeloid leukemia from single donors reveals RET as a potential therapeutic target.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq2000
Description
Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: Transcriptome of several AML cell lines
Publication Title
Modeling human MLL-AF9 translocated acute myeloid leukemia from single donors reveals RET as a potential therapeutic target.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: Transcriptome of normal cells (CD34+) from different donors
Publication Title
Modeling human MLL-AF9 translocated acute myeloid leukemia from single donors reveals RET as a potential therapeutic target.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaHiSeq2000
Description
Next generation DNA sequencing of acute myeloid leukemia (AML) patient samples has revealed novel recurrent mutations while at the same time highlighting the genetic heterogeneity of the disease. These observations suggest that an extraordinarily large number of combinations of mutations can contribute to leukemogenesis. In order to address the question of the contribution of patient genetic background to AML we have developed a model system to generate multiple human leukemias in a single donor’s genetic background. Stepwise RNA-seq data from this model shows that in the context of AML driven by the MLL-AF9 (MA9) oncogene, the genetic background of the donor does not have a detectable effect. Comparison of these model leukemias from multiple single donors to AML patient samples containing MA9 translocations revealed conserved gene expression patterns not previously highlighted in this genetic sub-type. We further demonstrate that the expression of one of these genes, RET, is essential both in vivo and in vitro growth of MA9 AMLs . Overall design: Transcriptome of MLL-AF9 AML pediatric patients
Publication Title
Modeling human MLL-AF9 translocated acute myeloid leukemia from single donors reveals RET as a potential therapeutic target.
Sample Metadata Fields
No sample metadata fields
View Samples