Reconstitution of female germ-cell development in vitro is a key challenge in reproductive biology and medicine. We show here that female (XX) embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in mice are induced into primordial germ cell-like cells (PGCLCs), which, when aggregated with female gonadal somatic cells as reconstituted ovaries, develop pre-meiotic germ cell characteristics, including X-reactivation, imprint erasure, and cyst formation. Upon transplantation under ovarian bursa, PGCLCs in the reconstituted ovaries mature into germinal vesicle-stage oocytes, which, through in vitro maturation and fertilization, contribute to fertile offspring. Our culture system serves as a robust foundation for the investigation of key properties of female germ cells, including the acquisition of totipotency, and for the reconstitution of whole female germ-cell development in vitro.
Offspring from oocytes derived from in vitro primordial germ cell-like cells in mice.
Sex, Specimen part
View SamplesEGFR tyrosine kinase inhibitors cause dramatic responses in EGFR-mutant lung cancer, but resistance universally develops. The involvement of -catenin in EGFR TKI resistance has been previously reported however the precise mechanism by which -catenin activation contributes to EGFR TKI resistance is not clear. Here, we show that EGFR inhibition results in the activation of -catenin signaling in a Notch3-dependent manner, which facilitates the survival of a subset of cells that we call adaptive persisters. We previously reported that EGFR-TKI treatment rapidly activates Notch3, and here describe the physical association of Notch3 with -catenin, leading to increased stability and activation of -catenin. We demonstrate that the combination of EGFR-TKI and a -catenin inhibitor inhibits the development of these adaptive persisters, decreases tumor burden, improves recurrence free survival, and overall survival in xenograft models. These results supports combined EGFR-TKI and -catenin inhibition in patients with EGFR mutant lung cancer.
Notch3-dependent β-catenin signaling mediates EGFR TKI drug persistence in EGFR mutant NSCLC.
Specimen part, Cell line
View SamplesInfection with non-cytopathic bovine viral diarrhea virus (ncpBVDV) is associated with uterine disease and infertility. This study investigated the influence of ncpBVDV on immune functions of the bovine endometrium by testing the response to bacterial lipopolysaccharide (LPS) at the level of whole-transcriptomic gene expression. Analysis showed that approximately 30% of the 1,006 genes altered by LPS are involved in immune response. Many innate immune genes that typically respond to LPS were inhibited by ncpBVDV including those involved in pathogen recognition, inflammation, interferon response, chemokines, tissue remodeling, cell migration and cell death/survival. Infection with ncpBVDV can thus compromise immune function and pregnancy recognition thereby potentially predisposing infected cows to postpartum bacterial endometritis and reduced fertility.
Global transcriptomic profiling of bovine endometrial immune response in vitro. I. Effect of lipopolysaccharide on innate immunity.
Sex, Treatment
View SamplesCommercially available cell lines derived from Head and Neck Squamous cell carcinoma (HNSCC) were cultured and baseline gene expression values were assayed.
Investigation of radiosensitivity gene signatures in cancer cell lines.
No sample metadata fields
View SamplesThe B1 SOX transcription factors SOX1/2/3/19 have been implicated in various processes of early embryogenesis. However, their regulatory functions in stages from the blastula to early neurula remain largely unknown, primarily because loss-of-function studies have not been informative to date. In our present study, we systematically knocked down the B1 sox genes in zebrafish. Only the quadruple knockdown of the four B1 sox genes sox2/3/19a/19b, which are active in the early embryo, resulted in very severe developmental abnormalities, confirming that the B1 sox genes are functionally redundant. We characterized the sox2/3/19a/19b quadruple knockdown embryos in detail by examining the changes in gene expression through microarray analysis as well as in situ hybridization.
B1 SOX coordinate cell specification with patterning and morphogenesis in the early zebrafish embryo.
Specimen part
View SamplesPericytes confer vascular stability in the retina, and the loss of pericytes can cause the blood-retina barrier breakdown seen in diabetic retinopathy. To identify endothelial-specific genes expressed in pericyte-deprived retinal vessels, we purified genetically labeled endothelial cells from Tie2-GFP transgenic mice treated with neutralizing antibody against PDGFRb (APB5) and performed gene expression profiling using DNA microarray. To find out endothelial-specific genes associated with the loss of pericyte coverage, the comparison of microarray data was carried out between retinal endothelial cells (data from GSE27238) and APB5-treated retinal endothelial cells.
Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown.
Specimen part
View SamplesAllergen exposure induces the airway epithelium to produce chemoattractants, proallergic interleukins, matrix-modifying proteins, and proteins that influence the growth and activation state of airway structural cells. These proteins, in turn, contribute to the influx of inflammatory cells and changes in structure that characterize the asthmatic airway. To use the response of the airway epithelium to allergen to identify genes not previously associated with allergic responses, we compared gene expression in cytokeratin-positive cells before and after segmental allergen challenge. After challenge with concentrations of allergen in the clinically relevant range, 755 (6%) of the detectable sequences had geometric mean fold-changes in expression, with 95% confidence intervals that excluded unity. Using a prospectively defined conservative filtering algorithm, we identified 141 sequences as upregulated and eight as downregulated, with confirmation by conventional polymerase chain reaction in all 10 sequences studied. Using this approach, we identified asthma-associated sequences including interleukin (IL-)-3, IL-4, and IL-5 receptor subunits, the p65 component of nuclear factor-kappaB, and lipocortin. The genomic response of the human airway to concentrations of allergen in the clinically relevant range involves a greater number of genes than previously recognized, including many not previously associated with asthma that are differentially expressed after airway allergen exposure.
Effects of allergen challenge on airway epithelial cell gene expression.
No sample metadata fields
View SamplesValidation of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease would provide an important resource for suggesting and testing of novel target-based therapies against this devastating cancer. In this study, comprehensive gene expression profiling in a novel orthotopic rat model of intrahepatic cholangiocarcinoma progression was carried out in an effort to identify potential therapeutic targets relevant to the progressive human cancer.
Intrahepatic cholangiocarcinoma progression: prognostic factors and basic mechanisms.
Sex, Specimen part
View SamplesGene expression in E coli W3110 strains with either ybaO over-expression (W3110/pcutR) or ybaO deletion (W3110/cutR) were measured with cysteine challenge.
Anaerobic Cysteine Degradation and Potential Metabolic Coordination in Salmonella enterica and Escherichia coli.
No sample metadata fields
View SamplesAnalysis to find splicing variants that are differentially expressed in a highly metastatic stomach cancer cell line, MKN45P, versus its parental cell line, MKN45
Identification of a novel protein isoform derived from cancer-related splicing variants using combined analysis of transcriptome and proteome.
Specimen part, Cell line
View Samples