TAZ-deficient mice have the abnormalities in the lung development. We expect the comparison of the gene expression profiles of TAZ-deficient and wild-type lungs would reveal the underlying mechanisms.
Transcriptional coactivator with PDZ-binding motif is essential for normal alveolarization in mice.
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DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.
Sex, Specimen part
View SamplesEmbryogenesis is tightly regulated by multiple levels of epigenetic systems such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent reprogramming occurs by de novo methylation and demethylation. Variance of DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analysed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions in the three germ layers and in the three adult somatic tissues are shared in common. This commonly methylated gene set is enriched in germ cell associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns with global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Taken together, our findings indicate that differentiation from ES cells to the three germ layers is accompanied by an increase in the number of commonly methylated DNA regions and that these tissue-specific alterations are present for only a small number of genes. Our findings indicate that DNA methylation at the proximal promoter regions of commonly methylated genes act as an irreversible mark which fixes somatic lineage by repressing transcription of germ cell specific genes.
DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.
Sex, Specimen part
View SamplesOsteosarcoma (OS) is the malignant bone tumor with a high tendency to metastasize to the lung, where the molecular mechanisms are unclear. The mouse OS cell line LM8 has been isolated originally from the Dunn OS cell line by in vivo selection as a subline with a high metastatic potential to the lung.
Stable knockdown of S100A4 suppresses cell migration and metastasis of osteosarcoma.
Cell line
View SamplesEpigenetically silenced Ink4a-Arf locus is activated by loss of H3K27me3 in cellular senescence, where secreted factor expression is also involved. Here we analyzed epigenome and transcriptome alteration during Ras-induced senescence using mouse embryonic fibroblast (MEF). Seventeen genes with H3K27me3 loss and H3K4me3 gain showed marked upregulation, including p16Ink4a and Bmp2, a secreted factor for BMP/SMAD signal. Smad6, specific BMP/SMAD pathway inhibitor, was identified as the only one gene showing de novo H3K27 trimethylation with H3K4me3, resulting in strong repression. Ras-activated cells senesced with SMAD1/5/8 phosphorylation, and they escaped from senescence with decreased SMAD1/5/8 phosphorylation when introducing Smad6 or knocking-down Bmp2.
Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence.
Specimen part, Treatment
View SamplesThe cellular ontogeny of hematopoietic stem cells (HSCs) remains poorly understood because their isolation from and their identification in early developing small embryos are difficult. We attempted to dissect early developmental stages of HSCs using an in vitro mouse embryonic stem cell (ESC) differentiation system combined with inducible HOXB4 expression. Here we report the identification of pre-HSCs and an embryonic type of HSCs (embryonic HSCs) as intermediate cells between ESCs and HSCs. Both pre-HSCs and embryonic HSCs were isolated by their c-Kit+CD41+CD45- phenotype. Pre-HSCs did not engraft in irradiated adult mice. After co-culture with OP9 stromal cells and conditional expression of HOXB4, pre-HSCs gave rise to embryonic HSCs capable of engraftment and long-term reconstitution in irradiated adult mice. Blast colony assays revealed that most hemangioblast activity was detected apart from the pre-HSC population, implying the early divergence of pre-HSCs from hemangioblasts. Gene expression profiling suggests that a particular set of transcripts closely associated with adult HSCs is involved in the transition of pre-HSC to embryonic HSCs.
Stepwise development of hematopoietic stem cells from embryonic stem cells.
Treatment
View SamplesWe observed the effects of TDAG8-overexpression in Lewis lung carcinoma (LLC) cells on the gene expression pattern.
The G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) facilitates tumor development by serving as an extracellular pH sensor.
Specimen part
View SamplesTarget genes of Fbxl10 during 3T3-L1 adipogenesis was analyzed
The FBXL10/KDM2B scaffolding protein associates with novel polycomb repressive complex-1 to regulate adipogenesis.
Cell line, Treatment
View SamplesEpigenetic gene regulation in various oncogenic pathways is currently an important focus of cancer research. The PI3K pathway plays a pivotal role in hepatocellular carcinoma, but the significance of histone modification in the PI3K pathway-dependent hepatotumorigenesis remains unknown.
Impact of histone demethylase KDM3A-dependent AP-1 transactivity on hepatotumorigenesis induced by PI3K activation.
Specimen part
View SamplesRetinoid X receptor (RXR)-gamma is a nuclear receptor-type transcription factor expressed mostly in the skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXR-gamma in the skeletal muscle (RXR-gamma mice), which showed lower blood glucose than the control mice. We used microarrays to investigate their glucose metabolism gene expression change.
Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRγ in skeletal muscle.
Sex, Age
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