We purified by magnet assisted cell sorting microglial cells from brains of adult Rab7 null mutant, aged mice and respective controls, isolated total RNA and performed RNAseq to determine the transciptome profiles. Overall design: Examination of transcriptomes of Rab7 null mutants and control (2 replicates each) and aged mice and young controls (3 replicates each)
Age-related myelin degradation burdens the clearance function of microglia during aging.
Age, Specimen part, Cell line, Subject
View SamplesEwings sarcoma is highly malignant bone tumor that involves childhood and adolescent, and its nature has not been well understood. To clarify its cellular origin and the mechanisms of tumorigenesis, we used ex vivo approach to create a murine model for Ewings sarcoma. The osteochondrogenic progenitors derived from the embryonic superficial zone (eSZ, designated as FZ in the data set) of murine long bones at late gestation were purified by microdissection, introduced with EWS-FLI1 or EWS-ERG retroviruses and transplanted into nude mice. Ewings sarcoma-like small round cell sarcoma developed at 100% penetrance, whereas tumor induction was less effective when growth place (GP)-derived cells were used. The different response of gene expression to EWS-FLI1 between eSZ and GP cells suggests importance of the specific cellular context for EWS-FLI1 to induce Ewings sarcoma. The Wnt/-catenin pathway was involved in close relationship to the cellular context, with Dkk2 and Wipf1 as important downstream modulators. Furthermore, gene expression profiling revealed similarity between our models and human Ewings sarcoma. These results indicate that Ewings sarcoma originates from the embryonic osteochondrogenic progenitor.
Ewing's sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors.
Specimen part, Time
View SamplesEwings sarcoma is highly malignant bone tumor that involves childhood and adolescent, and its nature has not been well understood. To clarify its cellular origin and the mechanisms of tumorigenesis, we used ex vivo approach to create a murine model for Ewings sarcoma. The osteochondrogenic progenitors derived from the facial zone (FZ) of murine long bones at late gestation were purified by microdissection, introduced with EWS-FLI1 or EWS-ERG retroviruses and transplanted into nude mice. Ewings sarcoma-like small round cell sarcoma developed at 100% penetrance, whereas tumor induction was less effective when growth place (GP)-derived cells were used. The different response of gene expression to EWS-FLI1 between FZ and GP cells suggests importance of the specific cellular context for EWS-FLI1 to induce Ewings sarcoma. The Wnt/-catenin pathway was involved in close relationship to the cellular context, with Dkk2 and Wipf1 as important downstream modulators. Furthermore, gene expression profiling revealed similarity between our models and human Ewings sarcoma. These results indicate that Ewings sarcoma originates from the embryonic osteochondrogenic progenitor.
Ewing's sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors.
Specimen part
View SamplesPhosphatidylcholine transfer protein (PC-TP, a.k.a StarD2) is abundantly expressed in liver and is regulated by PPAR. When fed the synthetic PPAR ligand fenofibrate, Pctp-/- mice exhibited altered lipid and glucose homeostasis. Microarray profiling of liver from fenofibrate fed wild type and Pctp-/- mice revealed differential expression of a broad array of metabolic genes, as well as their regulatory transcription factors. Because its expression controlled the transcriptional activities of both PPAR and HNF4 in cell culture, the broader impact of PC-TP on nutrient metabolism is most likely secondary to its role in fatty acid metabolism.
Regulatory role for phosphatidylcholine transfer protein/StarD2 in the metabolic response to peroxisome proliferator activated receptor alpha (PPARalpha).
Sex, Age, Specimen part
View SamplesInnate immune sensing of influenza A virus (IAV) induces activation of various immune effector mechanisms including the NLRP3 inflammasome and programmed cell death pathways. Although type I IFNs are identified as key mediators of inflammatory and cell death responses during IAV infection, the involvement of various IFN-regulated effectors in facilitating these responses are less studied. Here, we demonstrate the role of interferon regulatory factor 1 (IRF1) in promoting NLRP3 inflammasome activation and cell death during IAV infection. IRF1 functions as a transcriptional regulator of Z-DNA binding protein 1 (ZBP1, also called as DLM1/DAI), a key molecule mediating IAV-induced inflammatory and cell death responses. Therefore, our study identified IRF1 as an upstream regulator of NLRP3 inflammasome and cell death during IAV infection and further highlights the complex and multilayered regulation of key molecules controlling inflammatory response and cell fate decisions during infections.
IRF1 Is a Transcriptional Regulator of ZBP1 Promoting NLRP3 Inflammasome Activation and Cell Death during Influenza Virus Infection.
Specimen part
View SamplesWe used RNA-seq to interrogate prostate cancer specific gene fusions, alternative splicings, somatic mutations and novel transcripts. Overall design: We sequenced the transcriptome (polyA+) of 20 prostate cancer tumors and 10 matched normal tissues using Illumina GAII platform. Then we used bioinformatic approaches to identify prostate cancer specific aberrations which include gene fusion, alternative splicing, somatic mutation, etc.
Recurrent chimeric RNAs enriched in human prostate cancer identified by deep sequencing.
No sample metadata fields
View SamplesThe in-vitro analysis of the hypomethylation of the imprinting control region 1 (ICR1) within the IGF2/H19 locus is challenged by the mosaic distribution of the epimutation in tissues from children with Silver-Russell syndrome (SRS).
Decreased expression of cell proliferation-related genes in clonally derived skin fibroblasts from children with Silver-Russell syndrome is independent of the degree of 11p15 ICR1 hypomethylation.
Specimen part, Disease
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
View SamplesTo gain insights into the genes whose expression levels are altered during stromal cell differentiation (decidualization), gene microarray profiling was performed following the experimentally induced decidualization protocol.
Rac1 Regulates Endometrial Secretory Function to Control Placental Development.
Sex, Specimen part, Treatment
View Samples