This SuperSeries is composed of the SubSeries listed below.
Cell-autonomous function of Runx1 transcriptionally regulates mouse megakaryocytic maturation.
Specimen part
View SamplesRUNX1 transcription factor (TF) is a key regulator of megakaryocytic development and when mutated is associated with familial platelet disorder and predisposition to acute myeloid leukemia (FPD-AML). We used mice lacking Runx1 specifically in megakaryocytes (MKs) to characterize the Runx1-mediated transcriptional program during advanced stages of MK differentiation. Gene expression and chromatin-immunoprecipitation-sequencing (ChIP-seq) of Runx1 andp300identified functional Runx1-bound MK enhancers. Runx1/p300 co-bound regions showed significant enrichment in genes important for MK and platelet homeostasis. Runx1-bound regions were highly enriched in RUNX and ETS motifs and to a lesser extent in GATA motif.The data providesthe first example of genome-wide Runx1/p300 occupancy in maturating FL-MK,unravels the Runx1-regulated program controlling MK maturationin vivoandidentifies itsbona fideregulated genes. It advances our understandingof the molecular events that upon mutations in RUNX1 lead to thepredisposition to familial platelet disorders and FPD-AML.
Cell-autonomous function of Runx1 transcriptionally regulates mouse megakaryocytic maturation.
Specimen part
View SamplesTo gain insight into the signaling pathway(s) required for ABL1/ABL2-dependent bone metastasis, we evaluated the consequences of single or double inactivation of ABL1 and ABL2 on the transcriptome of breast cancer cells. Double ABL1/ABL2 knockdown was required to decrease the levels of p-CrKL by more than 90%, indicative of inactivation of the endogenous ABL kinases. To examine the consequences of depleting the ABL kinases on the transcriptome of metastatic breast cancer cells we employed next generation sequencing (RNAseq) analysis. We found that 180 genes were significantly down-regulated and 40 genes were significantly up-regulated in ABL1/ABL2 knockdown cells. Overall design: Four samples were analyzed control, Abl single knockdown, Arg single knockdown, Abl/Arg double knockdown. Experiments were performed in triplicate.
ABL kinases promote breast cancer osteolytic metastasis by modulating tumor-bone interactions through TAZ and STAT5 signaling.
No sample metadata fields
View SamplesWe report the single base pair analysis of the ocular transcriptome from wild type and BC027072 knockout animals. Comparison was analyzed to understand gene expression changes in a mouse model for early onset retinal degeneration which phenocopies a human form of autosomal recessive retinitis pigmentosa Overall design: Eye mRNA profiles were generated from 3 week-old C57BL/6J and BC027072 -/- in triplicate and sequenced using the Illumina HiSeq 2500
Animals deficient in C2Orf71, an autosomal recessive retinitis pigmentosa-associated locus, develop severe early-onset retinal degeneration.
No sample metadata fields
View SamplesAGO-PAR-CLIP was employed to identify microRNA binding sites in BCBL-1, a Kaposi's sarcoma-associated herpesvirus (KSHV) infected B-cell line and DG75, a KSHV negative B-cell line as a control. By using our novel computational method (PARma) and differential analysis of PAR-CLIP data, highly accurate target sites of KSHV microRNAs can be defined. Overall design: Examination of microRNA target sites in two different cell lines using replicate PAR-CLIP experiments
PARma: identification of microRNA target sites in AGO-PAR-CLIP data.
Cell line, Subject
View SamplesEffect of JMT overexpression in global gene expression
Complement analysis of xeroderma pigmentosum variants.
No sample metadata fields
View SamplesWe analyzed small RNAs from three mammalian species, and found that in all these species piRNA-directed targeting is accompanied by the generation of short sequences that have a very precisely defined length and a specific spatial relationship with the guide piRNAs. Overall design: small RNA-seq of testes lysate (beta-eliminated)
Conserved generation of short products at piRNA loci.
No sample metadata fields
View SamplesRelative contribution of sequence and structural features to the mRNA-binding of Argonaute/miRNA complexes and the degradation of miRNA targets
Relative contribution of sequence and structure features to the mRNA binding of Argonaute/EIF2C-miRNA complexes and the degradation of miRNA targets.
No sample metadata fields
View SamplesIn mice, seminal fluid elicits an inflammation-like response in the female genital tract that activates immune adaptations to advance the likelihood of conception and pregnancy. Here we examined whether similar changes in leukocyte and cytokine parameters occur in the human cervix in response to the male partners seminal fluid. After a period of abstinence in proven-fertile women, duplicate sets of biopsies were taken from the ectocervix in the peri-ovulatory period and again 48 h later, 12 h after unprotected vaginal coitus, vaginal coitus with use of a condom, or no coitus. One pair of first biopsy and second biopsy RNA samples from each treatment group were reverse transcribed into cDNA and hybridized to Affymetrix Human Gene 1.0 ST arrays. A total of 713 probe sets were identified as differentially expressed (fold change >2) between first and second biopsies after unprotected coitus, with 436 genes upregulated and 277 genes downregulated. Ingenuity Pathway Analysis revealed that gene pathways including inflammatory response, immune response, immune cell trafficking, cellular movement and antigen presentation were significantly affected by seminal fluid exposure. Amongst these were genes encoding several chemokines which target granulocytes, monocyte/macrophages, dendritic cells and lymphocytes, proinflammatory cytokines and regulators of cytokine synthesis, prostaglandin pathway gene including PTGS2; COX-2) and several matrix metalloproteinases (MMPs). Of these genes, no change or a substantially smaller change was seen between first and second biopsies obtained after coitus with condom use, or abstinence. An increase in CSF2, IL6, IL8 and IL1A expression was confirmed by qRT-PCR in larger sets of duplicate biopsies (n=6-7 per group). We conclude that seminal fluid introduced at intercourse elicits expression of pro-inflammatory cytokines and chemokines which underpins the accompanying recruitment of macrophages, dendritic cells and memory T cells. The leukocyte and cytokine environment induced in the cervix by seminal fluid appears competent to initiate adaptations in the female immune response that promote fertility. This response is also relevant to transmission of sexually transmitted pathogens, and potentially susceptibility to cervical metaplasia.
Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus.
Treatment
View SamplesThis dataset is part of the manuscript titled "The metabolic regulator ERRalpha, a downstream target of HER2/IGF1, as a therapeutic target in breast cancer" (in review). The expression data obtained in human mammary epithelial cells were used to generate a list of ERRalpha-regulated genes that was later refined in clinical breast cancer datasets to generate a clinically relevant signature of ERalpha activity (referred to as Cluster 3 signature). Using this signature of the estrogen-related receptor alpha (ERRa) to profile more than eight-hundred breast tumors, we found that patients with tumors exhibiting higher ERRa activity were predicted to have shorter disease free survival. Further, the ability of an ERRa antagonist, XCT790, to inhibit breast cancer cell proliferation correlates with the cells intrinsic ERRa activity. These findings highlight the potential of using the ERRa signature and antagonists in targeted therapy for breast cancer. Using a chemical genomic approach we determined that activation of the HER2/IGF1 signaling pathways upregulates the expression of PGC-1b, an obligate cofactor for ERRa activity. Knockdown of PGC-1b in HER2 positive breast cancer cells impaired ERRa signaling and reduced cell proliferation, implicating a functional role of PGC1b/ERRa in the pathogenesis HER2 positive breast cancer.
The metabolic regulator ERRα, a downstream target of HER2/IGF-1R, as a therapeutic target in breast cancer.
Specimen part
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