RNA expression analysis was performed to compare patterns to DNA copy number changes and sensitivity to BCL2 inhibitors.
Integrative genomic analysis of small-cell lung carcinoma reveals correlates of sensitivity to bcl-2 antagonists and uncovers novel chromosomal gains.
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Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation.
Sex, Specimen part
View SamplesPreimplantation embryos undergo a transient wave of genome-wide demethylation with the exception of imprinted genes that are critical for fetal development. Here we show that the derivation of female mouse embryonic stem cells (ESCs) in the presence of inhibitors of MEK1/2 and Gsk3 (2i-ESCs), known as 2i or ground-state culture conditions, results in a widespread loss of DNA methylation including a massive erasure of genomic imprints. In this study, we analyzed global gene expression profile and global DNA methylation status in 2i-ESCs and 2i-ESCs derived differentiated cells. S-ESCs are ESCs established under serum-containing medium. 2i_S_ESCs are ESCs established in 2i-containing medium, followed by maintenance in serum-containing medium.
Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An EWS-FLI1-Induced Osteosarcoma Model Unveiled a Crucial Role of Impaired Osteogenic Differentiation on Osteosarcoma Development.
Specimen part, Cell line, Treatment
View SamplesEWS-FLI1, a multi-functional fusion oncogene, is exclusively detectable in Ewing sarcomas. However, previous studies reported that a subset of osteosarcomas also harbor EWS-ETS family fusion, suggesting that the fusion gene may be involved in the development of a particular type of osteosarcomas. Here using the doxycycline inducible EWS-FLI1 system, we established an EWS-FLI1-dependent osteosarcoma model from murine bone marrow stromal cells. We revealed that the withdrawal of EWS-FLI1 expression enhances the osteogenic differentiation of sarcoma cells, leading to mature bone formation. Taking advantage of induced pluripotent stem cell (iPSC) technology, we also showed that the sarcoma-derived iPSCs with cancer-related genetic abnormalities exhibited the impaired differentiation program of osteogenic lineage irrespective of the EWS-FLI1 expression. Finally, we demonstrated that EWS-FLI1 contributed to in vitro sarcoma development from the sarcoma-iPSCs after osteogenic differentiation. These findings demonstrated that modulating cellular differentiation is fundamental principle of the EWS-FLI1-induced osteosarcoma development. Furthermore, the in vitro cancer model using sarcoma-iPSCs should provide a novel platform for dissecting relationship between cancer genome and cellular differentiation.
An EWS-FLI1-Induced Osteosarcoma Model Unveiled a Crucial Role of Impaired Osteogenic Differentiation on Osteosarcoma Development.
Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Human β-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF.
Specimen part, Treatment, Time
View SamplesWe examine the global effect of hBD3 on transcription in TLR4-stimulated macrophages and for the first time show that hBD3 inhibits the transcription of critical pro-inflammatory genes.
Human β-defensin 3 affects the activity of pro-inflammatory pathways associated with MyD88 and TRIF.
Specimen part, Treatment, Time
View SamplesGene expression profiling for identification of genes regulated by DNA methylation
Genome-wide screening of genes regulated by DNA methylation in colon cancer development.
Specimen part, Cell line
View SamplesThe spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect of the genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an Apc Min/+ mouse model, in which the loss of the Apc gene plays a critical role in tumor development, and established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in the RTCs that were affected by the Apc mutations did not overlap with the genes that were affected in the intestine or those that were affected by the accumulation of beta-catenin in PSCs. The RTCs lacked pluripotency but exhibited the increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. The genetic rescue of the mutated Apc allele conferred pluripotency on the RTCs and enabled their differentiation into various cell types in vivo. The re-disruption of Apc in the RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, yet the majority of intestinal lesions remained pre-tumoral microadenomas. These results highlight the significant influence of the cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on colon tumor promotion.
Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
EWS/ATF1 expression induces sarcomas from neural crest-derived cells in mice.
Specimen part
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