Transcriptomes of mouse E12.5 primordial germ cells (PGCs), primordial germ cell-like cells (PGCLCs) isolated from 6-day culture embryoid bodies, and the precursor pluripotent stem cells [embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)] and epiblast-like cells (EpiLCs)
Erasure of DNA methylation, genomic imprints, and epimutations in a primordial germ-cell model derived from mouse pluripotent stem cells.
Sex, Specimen part
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Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs.
Specimen part
View SamplesMulticellular organisms consist of multiple cell types, whose identities are maintained appropriately at locations where they are reside. The identity of each cell type is primarily maintained by cell-type-specific gene expression programs, but mechanisms that suppress these programs are poorly defined. Here we show that serum response factor (Srf), a transcription factor that is activated by various extracellular stimuli, can repress cell-type-specific genes and promote cellular reprogramming to pluripotency. Manipulations that decrease -actin monomer resulted in nuclear accumulation of Mkl1 and the activation of Srf, which downregulated cell-type-specific genes and altered epigenetics in enhancers and chromatin organization. Mice overexpressing Srf exhibited various pathologies including an ulcerative colitis-like symptom and a metaplasia-like phenotype in the pancreas. Our results demonstrate an unexpected function of Srf via a mechanism by which extracellular stimuli actively destabilize cell identity and suggest Srf involvement in a wide range of diseases.
Srf destabilizes cellular identity by suppressing cell-type-specific gene expression programs.
Specimen part
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Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation.
Specimen part
View SamplesWe report a reprogrammable mouse system in which reprogramming factor expression in vivo can be controlled temporally by treatment with doxycycline (Dox). Transient expression of reprogramming factors in vivo results in tumor development in various tissues, consisting of undifferentiated dysplastic cells. We analyzed the kidney tumors developed in reprogrammable mice for global gene expressions and DNA methylations.
Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
OVOL2 Maintains the Transcriptional Program of Human Corneal Epithelium by Suppressing Epithelial-to-Mesenchymal Transition.
Specimen part, Cell line
View SamplesIn development, embryonic ectoderm differentiates into several lineages including neuroectoderm and surface ectoderm, through the mechanism largely unclear. Here we report that OVOL2 is required for the transcriptional program of corneal epithelium cell(CEC)s, a derivative of surface ectoderm, and it might regulates the differential transcriptional programs between the two lineages. By a functional screening, we identified transcription factors (TFs) maintaining human CECs. OVOL2 was necessary to maintain the transcriptional program in CECs, particularly through repressing expression of mesenchymal genes. OVOL2 combined with several TFs were able to activate the transcriptional program of CECs in fibroblasts, accompanied by induction of chromatin landscape. Moreover, our analysis revealed that neuroectoderm derivatives express some of mesenchymal genes. In fact, OVOL2 alone was able to induce the transcriptional program of CECs in neural progenitor cells (NPCs) through repression of mesenchymal genes as well as activation of epithelial genes. Our data suggest that the difference between the transcriptional programs of surface ectoderm-derivatives and neuroectoderm-derivatives is regulated in part by the reciprocally-repressive mechanism between epithelial and mesenchymal genes that is seen in epithelial-to-mesenchymal transition.
OVOL2 Maintains the Transcriptional Program of Human Corneal Epithelium by Suppressing Epithelial-to-Mesenchymal Transition.
Specimen part
View SamplesConventional anti-cancer drug screening is typically performed in the absence of accessory cells (e.g. stromal cells) of the tumor microenvironment, which can profoundly alter anti-tumor drug activity. To address this major limitation, we have developed assays (e.g. the tumor cell-specific in vitro bioluminescence imaging (CS-BLI) assay) to selectively quantify tumor cell viability, in presence vs. absence of non-malignant stromal cells or drug treatment. These assays have allowed us to identify that neoplastic cells from diverse malignancies exhibit stroma-induced resistance to different anti-tumor agents. In this analysis, we evaluated the molecular changes triggered in myeloma cells by their in vitro interaction with stromal cells. The transcriptional profile of 3 human multiple myeloma (MM) cell lines (MM.1S, MM.1R, INA-6) co-cultured with stromal cells vs. when cultured alone was characterized by oligonucleotide microarray analysis, using the human U133 plus 2.0 Affymetrix GeneChip.
Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity.
Cell line
View SamplesEstrogen signaling pathway is critical for breast cancer development and has remained the major adjuvant therapeutic target for this disease. Tamoxifen has been used in clinic for many years to treat ER-positive breast cancer. However a great many (30%) suffer relapse due to drug resistance. In this study, the bromodomain inhibitor JQ1 was found to down-regulate ERalpha gene expression and have anti-tumor effect in cultured tamoxifen-resisant breast cancer cells.
An epigenomic approach to therapy for tamoxifen-resistant breast cancer.
Cell line, Treatment
View SamplesWe previously found a short sleeper mutant, fmn, and identified its mutation in the dopamine transporter gene. In an attempt to discover additional sleep related genes in Drosophila, we carried out a microarray analysis comparing mRNA expression in heads of fmn and control flies and found differentially expressed genes.
The NMDA Receptor Promotes Sleep in the Fruit Fly, Drosophila melanogaster.
Sex, Specimen part
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