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
View SamplesEmergence of antiestrogen-resistant cells in MCF-7 cells during suppression of estrogen signaling is a widely accepted model of acquired breast cancer resistance to endocrine therapy. To obtain insight into the genomic basis of endocrine therapy resistance, we characterized MCF-7 monoclonal sublines that survived 21-day exposure to tamoxifen (T-series sublines) or fulvestrant (F-series sublines) and sublines unselected by drugs (U-series). All T/F-sublines were resistant to the cytocidal effects of both tamoxifen and fulvestrant. However, their responses to the cytostatic effects of fulvestrant varied greatly, and their remarkably diversified morphology showed no correlation with drug resistance. mRNA expression profiles of the U-sublines differed significantly from those of the T/F-sublines, whose transcriptomal responsiveness to fulvestrant was largely lost. A set of genes strongly expressed in the U-sublines successfully predicted metastasis-free survival of breast cancer patients. Most T/F-sublines shared highly homogeneous genomic DNA aberration patterns that were distinct from those of the U-sublines. Genomic DNA of the U-sublines harbored many aberrations that were not found in the T/F-sublines. These results suggest that the T/F-sublines are derived from a common monoclonal progenitor that lost transcriptomal responsiveness to antiestrogens as a consequence of genetic abnormalities many population doublings ago, not from the antiestrogen-sensitive cells in the same culture during the exposure to antiestrogens. Thus, the apparent acquisition of antiestrogen resistance by MCF-7 cells reflects selection of preexisting drug-resistant subpopulations without involving changes in individual cells. Our results suggest the importance of clonal selection in endocrine therapy resistance of breast cancer.
Antiestrogen-resistant subclones of MCF-7 human breast cancer cells are derived from a common monoclonal drug-resistant progenitor.
Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Frequent pathway mutations of splicing machinery in myelodysplasia.
Cell line
View SamplesIn this study, to obtain the biological impact of the mutated U2AF35, HeLa and TF-1 cells were retrovirally transduced with either mock, wild-type or S34F mutant of U2AF35, and Expression array was performed.
Frequent pathway mutations of splicing machinery in myelodysplasia.
Cell line
View SamplesIn this study, to obtain the biological impact of the mutated U2AF35, HeLa cells were retrovirally transduced with either mock, wild-type or S34F mutant of U2AF35, and Exon array was performed.
Frequent pathway mutations of splicing machinery in myelodysplasia.
Cell line
View SamplesUsing primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was confirmed using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 expression without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to separate stem and progenitor cells, RNA-seq identified unique gene signatures for the separate populations which may serve as biomarkers. Pathways enrichment in stem cells identified ribosome biogenesis and membrane estrogen-receptor signaling with NF?B signaling enriched in progenitors and these were biologically confirmed. Further, bioassays identified heightened autophagy flux and reduced metabolism in stem cells relative to progenitors. These approaches similarly identified cancer stem-like cells from prostate cancer specimens and prostate, breast and colon cancer cell lines suggesting wide applicability. Together, the present studies isolate and identify unique characteristics of normal human prostate stem cells and uncover processes that maintain stem cell homeostasis in the prostate gland. Overall design: Comparing RNA-seq gene profiles in label-retaining prostate stem cells and non-retaining progenitor cells
Isolation and functional interrogation of adult human prostate epithelial stem cells at single cell resolution.
Specimen part, Subject
View SamplesThe aim was to carry out global analysis of gene expression changes occurring in the normal pubertal mouse mammary gland from the appearance to the regression of terminal end buds.
ERalpha-CITED1 co-regulated genes expressed during pubertal mammary gland development: implications for breast cancer prognosis.
Sex, Age, 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
View SamplesClear cell sarcoma (CCS) is an aggressive soft tissue malignant tumor characterized by a unique t(12; 22) translocation, leading to the expression of a chimeric EWS/ATF1 fusion gene. However, little is known about the mechanisms underlying how EWS/ATF1 is involved in the development of CCSs. In addition, the cells of origin for CCSs remain to be determined. We generated EWS/ATF1-inducible mice, and examined the effects of EWS/ATF1 expression in adult cells. We show that the forced expression of EWS/ATF1 results in the development of EWS/ATF1-dependent sarcomas in mice. The histology of EWS/ATF1-induced sarcomas resembles that of CCSs and EWS/ATF1-induced tumor cells express CCS-markers, such as S100, Sox10, and Mitf. A lineage tracing experiment revealed that such sarcomas are derived from neural crest-lineage cells. Finally, we found that EWS/ATF1 directly induces Fos in an ERK-independent manner, and demonstrated that the increased Fos expression is important for the active cell proliferation in not only EWS/ATF1-induced sarcomas, but also in human CCSs. Our results indicate that FOS, as well as EWS/ATF1 itself, could be a promising therapeutic target for the treatment of EWS/ATF1-related sarcomas.
EWS/ATF1 expression induces sarcomas from neural crest-derived cells in mice.
Specimen part
View SamplesIn this study we tested the ability to predict organ injury from transcriptomics data in Sprague-Dawley rats at early time points after exposure to thioacetmide (8 and 24 hours). We selected thioacetamide, an organosulfur compound extensively used in animal studies as a hepatotoxin and carcinogen for its ability to cause acute liver damage. Overall design: We treated 30 Sprague-Dawley rats with saline solution (control), 25 mg/kg (low dose), and 100 mg/kg (high dose) to produce different degrees of injury. RNA samples for gene expression analysis were collected from the liver, kidney, and heart at 8 and 24 hours. Number of repicates were five.
Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data.
Specimen part, Cell line, Subject
View Samples