Autism spectrum disorder (ASD) is a disorder of brain development believed, in most cases, to be of genetic origin. We use induced pluripotent stem cells (iPSCs)-derived 3-dimensional neural cultures (organoids) in patients with ASD and macrocephaly to investigate neurodevelopmental alterations that cause this form of ASD. By using transcriptome analyses, we identified modules of co-expressed genes significantly upregulated in ASD patients compared to non-ASD first-degree family members. Overall design: Total RNA was prepared from terminal differentiation day 0, 11 and 31 of iPSCs-derived neural cultures from ASD patients and non-ASD first-degree family members. A total of 4 patients and 8 controls (unaffected family members) were analyzed in replicates (two to three iPSC clones per person).
FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders.
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View SamplesKeratinocyte growth factor (KGF, fibroblast growth factor-7) is a fibroblast-derived mitogen, which stimulates proliferation of epithelial cells. The expression of KGF by dermal fibroblasts is induced following injury and it promotes wound repair. However, the role of KGF in cutaneous carcinogenesis and cancer progression is not known. We have examined the role of KGF in progression of squamous cell carcinoma (SCC) of the skin.
Keratinocyte growth factor induces gene expression signature associated with suppression of malignant phenotype of cutaneous squamous carcinoma cells.
Specimen part, Disease
View SamplesThe role of on-CG methylation in seed development and dormancy remains unknown. There are four genes in charge of non-CG methylation in Arabidopsis: drm1, drm2, cmt2 and cmt3. The majority of non-CG methylation in vegetative tissues, leaf, is gone in homozygous ddcc mutant line (Hume et al., 2014). To uncover the possible role of non-CG DNA methylation in seed development and dormancy, we characterized the transcriptome of ddcc mutant in Arabidopsis post-mature green seeds using Illumina sequencing. Meanwhile, post-mature green seeds from wild type were used as control. Overall design: Illumina sequencing of transcripts from post-mature green seeds of ddcc mutant and wild type. Two biological replicates were collected.
Similarity between soybean and <i>Arabidopsis</i> seed methylomes and loss of non-CG methylation does not affect seed development.
Specimen part, Subject
View SamplesTumors driven by activation of the transcription factor Myc generally show oncogene addiction. However, the gene-expression programs that depend upon sustained Myc activity in those tumors remain unknown. We have addressed this issue in a model of liver carcinoma driven by a reversible tet-Myc transgene, combining gene expression profiling with the mapping of Myc and RNA Polymerase II on chromatin. Switching off the oncogene in advanced carcinomas revealed that Myc is required for the continuous activation and repression of distinct sets of genes, constituting no more than half of those deregulated during tumor progression, and an even smaller subset of all Myc-bound genes. We further showed that a Myc mutant unable to associate with the co-repressor protein Miz1 is defective in the initiation of liver tumorigenesis. Altogether, our data provide the first detailed analysis of a Myc-dependent transcriptional program in a fully developed carcinoma, revealing that the critical effectors of Myc in tumor maintenance must be included within defined subsets (ca. 1,300 each) of activated and repressed genes. Overall design: RNAseq samples of control liver (n=11), tet-Myc tumors (n=16), tet-Myc tumors with short-term Myc inactivation (n=8), tet-MycVD tumors (n=11)
Identification of MYC-Dependent Transcriptional Programs in Oncogene-Addicted Liver Tumors.
Specimen part, Cell line, Subject
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EphB2 Promotes Progression of Cutaneous Squamous Cell Carcinoma.
Specimen part, Cell line
View SamplesThe incidence of keratinocyte-derived skin cancer, cutaneous squamous cell carcinoma (cSCC) is increasing worldwide making it the second most common metastatic skin cancer.
EphB2 Promotes Progression of Cutaneous Squamous Cell Carcinoma.
Specimen part, Cell line
View SamplesThe role of Eph/ephrin signaling in numerous biological processes has been established. However, Eph/ephrin signaling has been shown to have complex role in tumor progression. The role of EphB2 receptor in the progression of cutaneous squamous cell carcinoma (cSCC) has not been studied before.
EphB2 Promotes Progression of Cutaneous Squamous Cell Carcinoma.
Cell line
View SamplesIt has been recently shown that N-ras plays a preferential role in immune cell development and function; specifically: N-ras, but not H-ras or K-ras, could be activated at and signal from the Golgi membrane of immune cells following a low level TCR stimulus. The goal of our studies was to test the hypothesis that N-ras and H-ras played distinct roles in immune cells at the level of the transcriptome.
In TCR-stimulated T-cells, N-ras regulates specific genes and signal transduction pathways.
Specimen part, Treatment
View SamplesOncogenic transformation in Ewing sarcoma tumors is driven by the fusion oncogene EWS-FLI1. The inducible expression of EWS-FLI1 (EF) in embryoid bodies, or collections of differentiating stem cells, generates cells with properties of Ewing sarcoma tumors, including characteristics of transformation. These cell lines exhibit anchorage-independent growth, a lack of contact inhibition and a strong Ewing sarcoma gene expression signature. These cells also demonstrate a requirement for the persistent expression of EWS-FLI1 for cell survival and growth.
Modeling the initiation of Ewing sarcoma tumorigenesis in differentiating human embryonic stem cells.
Specimen part
View SamplesThe production of Tobacco Acid Pyrophosphatase (TAP), an enzyme commonly used for the removal of the 5’cap of eukaryotic mRNAs, has been recently discontinued. Here we performed a comparison of current alternatives for the mapping of 5’cap mRNAs and the associated transcription start sites in Sacharomyces cerevisiae. Specifically we compared TAP with Cap-clip and a Decapping Pyrophosphohydrolase. Our results suggest that Cap-clip is a good alternative for TAP. Overall design: We used two biological replicates of S. cerevisiae that was grown to exponential phase (OD600 ~1) in rich media (YPAD). Samples where processed until the dephosphorylation step (CIP treatment). After that each sample was split in 4 aliquots: TAP treatment, Cap-Clip treatment, Decapping Pyrophosphohydrolase treatment or no treatment (negative control). From that step all samples are processed in parallel.
Widespread Co-translational RNA Decay Reveals Ribosome Dynamics.
Treatment, Subject
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