We report the physiological role of ATF4 within mouse liver, under basal and ER stress conditions. With three mice per group, and approximately 30 million reads per sample, we obtained genome-wide role of ATF4 within the liver. We find ATF4 is responsible for a small subset of ER stress genes, and larger than previously thought basal subset. Overall design: Examination of the loss of ATF4 basally and during 6 hour Tunicamycin induced ER stress
Transcription factor ATF4 directs basal and stress-induced gene expression in the unfolded protein response and cholesterol metabolism in the liver.
Specimen part, Cell line, Treatment, Subject
View SamplesOur previous studies have shown that C/EBP plays a critical role in human endometrial stromal decidualization. In order to identify the molecular pathways regulated by C/EBP during decidualization, we performed gene expression profiling using RNA isolated from normal and C/EBP-deficient human endometrial stromal cells. The microarray results revealed that several key regulators of stromal differentiation, such as BMP2, Wnt4, IL-11R and STAT3, operate downstream of C/EBP during decidualization. Further studies revealed that STAT3 is a direct target of C/EBP and plays an important role in cytokine signal during the decidualization process. Gene expression profiling, using STAT3-deficient HESCs, showed an extensive overlap of pathways downstream of STAT3 and C/EBP during stromal cell differentiation.
Regulation of human endometrial stromal proliferation and differentiation by C/EBPβ involves cyclin E-cdk2 and STAT3.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Specimen part, Treatment
View SamplesUlipristal acetate (UPA), also referred to as VA/CDB-2914, is a new and promising emergency contraceptive. It is a selective progesterone receptor modulator (SPRM) that has been approved in Europe and the USA for emergency contraception.
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Specimen part, Treatment
View SamplesPrevious studies have shown that PR is a critical regulator of ovulation. The PR-null mice (PRKO) failed to ovulate due to a failure in the rupture of the preovulatory follicles.
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Specimen part
View SamplesAscertain the effects of disease-causing gene mutations on the differentiation status of human nave CD4+ T cells in the setting of primary immunodeficiencies. Thus, do CD4+ T cells isolated according to a nave surface phenotype (ie CD4+CD45RA+CCR7+) from healthy donors exhibit a similar gene expression profile as phenotpyically-matched cells isolated from individuals with defined primary immunodeficiencies caused by specific monogenic mutations.
Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets.
Specimen part
View Samplesgene expression at 6h of differentiation of Human endometrial stromal cell expressing either or both of PRA and PRB
Roles of progesterone receptor A and B isoforms during human endometrial decidualization.
Specimen part, Treatment
View SamplesEstrogen and progesterone are important regulators of human endometrial differentiation. These steroid hormones act, at least in part, through their nucelar receptors. Role of estrogen receptor alpha (ESR1) during human endometrial differentiation is still unclear.
Roles of Estrogen Receptor-α and the Coactivator MED1 During Human Endometrial Decidualization.
Specimen part
View SamplesThe etiology of ovarian cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mouse model termed ERalpha d/d in which a conditional deletion of estrogen receptor alpha (ERalpha) gene occurred in the anterior pituitary, but ERalpha expression remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E) at the level of the pituitary led to elevated production of luteinizing hormone (LH) by this tissue. Hyperstimulation of ovarian cells by LH resulted in increased steroidogenesis, leading to high circulating levels of progesterone, testosterone and E. The ERalpha d/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age, and by 12 months, most mice carrying these tumors died. Besides proliferating epithelial cells, these tumors also contained an expanded population of stromal cells, which express P450 aromatase suggesting that these cells acquired the ability to synthesize E. In ERalpha d/d mice, in response to the E produced by the stromal cells, the ERalpha signaling is accentuated in the ovarian epithelial cells, triggering increased ERalpha-dependent gene expression, abnormal cell proliferation, and tumorigenesis. The ERalpha d/d animal model of ovarian epithelial tumorigenesis will serve as a powerful tool for exploring the involvement of E-dependent signaling pathways in the etiology of ovarian cancer.
Dysregulated estrogen receptor signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis in mice.
Sex, Age, Specimen part
View SamplesPlacenta development involves complex molecular and cellular interactions between the maternal endometrium and the developing embryo, however, it is not clear what are the precise mechanisms regulating this maternal-fetal crosstalk. Using genetic and cell biological approaches, we have demonstrated that Ras-related C3 botulinum toxin substrate 1 (Rac1), a maternal factor expressed in decidual cells and is markedly elevated in mouse decidua on days 7 and 8 of gestation, regulates the secretory pathways that mediate stromal-endothelial and stromal-trophoblast crosstalk within a narrow temporal window during placenta development.
Rac1 Regulates Endometrial Secretory Function to Control Placental Development.
Specimen part
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