MYCN-high and MYCN-low neuroblastoma cells differ in their responses to Doxorubicin treatment. To explain this difference we compared the global trancriptomes of MYCN-high and MYCN-low cells before, during and after treatment. Overall design: MYCN-high cells without doxycyline and MYCN-low cells with doxycycline were treated with 0.1µg/ml Doxorubicin. Transcriptome was measured for the following time points: in untreated cells, in cells which were treated with Doxorubicin for 72 hours, and in cells collected three, eight and fourteen days after Doxorubin washout. Experiment was performed in biological duplicate.
Cell-Cycle Position of Single MYC-Driven Cancer Cells Dictates Their Susceptibility to a Chemotherapeutic Drug.
Treatment, Subject, Time
View SamplesOur study in zebrafish is the first to use an animal model to understand the biology of the developmental disorder Roberts Syndrome (RBS). RBS is caused by mutations in the ESCO2 gene.
A zebrafish model of Roberts syndrome reveals that Esco2 depletion interferes with development by disrupting the cell cycle.
Age, Specimen part
View SamplesLymphocytes represent basic components of vertebrate adaptive immune systems, suggesting the utility of non-mammalian models to define the molecular basis of their development and differentiation. Our forward genetic screens in zebrafish for recessive mutations affecting early T cell development revealed several major genetic pathways. The identification of lineage-specific transcription factors and specific components of cytokine signaling and DNA replication/repair pathways known from studies of immuno-compromised mammals provided an evolutionary cross-validation of the screen design. Unexpectedly, however, certain pre-mRNA processing factor genes, including tnpo3, encoding a regulator of alternative splicing, were also found to play a specific role in early T cell development. In both zebrafish and mouse, TNPO3 deficiency impairs intrathymic T cell differentiation, illustrating evolutionarily conserved and cell type-specific functions of certain pre-mRNA processing factor. Overall design: Taking advantage of the apparent evolutionary conservation of lymphocyte-based immunity, we conducted genetic screens in zebrafish aimed at identifying novel regulators of T lymphocyte development. Apart from mutations in genes encoding lymphoid lineage-specific transcription factors, and components of cytokine signaling and DNA replication/repair pathways, mutations in genes encoding pre-mRNA processing factors were also found. To examine the molecular consequences, transcriptome analyses were conducted for three mutants, snapc3, lsm8, tnpo3.
Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways Regulating Early T Cell Development.
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