Objective: Analyze expression patterns of genes located at linkage region of SPOAN syndrome (11q12-13), in order to identify genes differentially expressed in samples of SPOAN individuals compared to healthy controls.
Overexpression of KLC2 due to a homozygous deletion in the non-coding region causes SPOAN syndrome.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons.
Specimen part
View SamplesiPSC were obtained from DPC from TRPC6-mut patient, a idiopathic autistic patient and a control. Original DPC and iPSC obtained were submited to expression analysis in order to check if the expression pattern obtained for the iPSC cells were closer related to embyonic cells than to the original DPC
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons.
Specimen part
View SamplesAs TRPC6 channel induces CREB-mediated trancription, Dental pulp cells from TRPC6-mut patient and from 6 controls were analyzed in order to verify if the disruption of TRPC6 leads to transcriptional changes.
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons.
Specimen part
View SamplesThe characteristics of immune cells infiltrating pediatric brain tumors is largely unexplored. A better understanding of these characteristics will provide a foundation for development of immunotherapy for pediatric brain tumors.
Characterization of distinct immunophenotypes across pediatric brain tumor types.
Specimen part, Disease, Disease stage
View SamplesPrevious studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild type PR, but with significantly reduced latency (median leukemia-free survival of 274 days versus 473 days for wild type PR, p<0.001). Resistance to proteolysis may increase the abundance of full length PR protein in early myeloid cells, and our previous data suggested that non-cleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.
A protease-resistant PML-RAR{alpha} has increased leukemogenic potential in a murine model of acute promyelocytic leukemia.
Cell line
View SamplesWe compared molecular characteristics of primary and recurrent pediatric ependymoma to identify sub-group specific differences.
Molecular sub-group-specific immunophenotypic changes are associated with outcome in recurrent posterior fossa ependymoma.
Specimen part
View SamplesInflammatory response has been identified as a molecular signature of high-risk Group A ependymoma (EPN). To better understand the biology of this phenotype and aid therapeutic development, transcriptomic data from Group A and B EPN patient tumor samples, and additional malignant and normal brain data, were analyzed to identify the mechanism underlying EPN group A inflammation.
Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma.
Specimen part, Disease, Disease stage
View SamplesTo better understand the pathogenesis of acute promyelocytic leukemia (APL, FAB M3 AML), we identified genes that are expressed differently in APL cells compared to other acute myeloid leukemia subtypes, and to normal promyelocytes. Comparative gene expression analysis of 14 M3, 62 other AML (M0, M1, M2 and M4) and 5 enriched normal promyelocyte samples revealed a signature of 1,121 genes that are specifically dysregulated in M3 samples relative to other AML, and that do not simply represent normal promyelocyte expression (M3-specific signature). We used a novel, high throughput digital platform (Nanostring's nCounter system) to evaluate a subset of the most significantly dysregulated genes in 30 AML samples; 33 of 37 evaluable gene expression patterns were validated. In an additional analysis, we selected only genes that are dysregulated in M3 both compared to other AML subtypes, and to purified normal CD34+ cells, promyelocytes, and/or neutrophils, thereby isolating a 478 gene "composite M3 dysregulome". Surprisingly, the expression of only a few of these genes was significantly altered in PR-9 cells after PML-RARA induction, suggesting that most of these genes are not direct targets of PML-RARA. Comparison of the M3-specific signature to our previously described murine APL dysregulome revealed 33 commonly dysregulated genes, including JUN, EGR1, and TNF. Collectively, these results suggest that PML-RARA initiates a transcriptional cascade which generates a unique downstream expression signature in both primary human and mouse APL cells.
High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples.
Sex, Race
View SamplesEstablishment of an in vitro system to explore molecular mechanisms of mastitis susceptibility in cattle by comparative expression profiling of Escherichia coli and Staphylococcus aureus inoculated primary cells sampled from cows with different genetic predisposition for somatic cell score
Comparative expression profiling of E. coli and S. aureus inoculated primary mammary gland cells sampled from cows with different genetic predispositions for somatic cell score.
Disease, Treatment, Time
View Samples