Post-transcriptional gene regulation by miRNAs and RNA binding proteins (RBP) is important in development, physiology and disease. To examine the interplay between miRNAs and the RBP ELAVL1 (a.k.a. HuR), we mapped miRNA binding sites on a transcriptome-wide scale in WT and Elavl1 knockout murine bone marrow-derived macrophages. Proximity of ELAVL1 binding sites attenuated miRNA binding to transcripts and promoted gene expression. Transcripts that regulate angiogenesis and macrophage/ endothelial cross talk were preferentially targeted by miRNAs, suggesting that ELAVL1 promotes angiogenesis, at least in part, by antagonism of miRNA function. We found that ELAVL1 antagonized binding of miR-27 to the 3'UTR of Zfp36 mRNA and alleviated miR-27-mediated suppression of the RBP ZFP36 (a.k.a. Tristetraprolin). Thus the miR-27-regulated mechanism synchronizes the expression of ELAVL1 and ZFP36. This study provides a resource for systems-level interrogation of post-transcriptional gene regulation in macrophages, a key cell type in inflammation, angiogenesis and tissue homeostasis. Overall design: Bone marrow derived macrpohges mRNA profiles of 7-day cultured wild type (WT) and Elavl1l-/- mouse bone marrow cells were generated by deep sequencing, with 4 biologic duplication, using Illumina GAII.
ELAVL1 modulates transcriptome-wide miRNA binding in murine macrophages.
No sample metadata fields
View SamplesThe concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease.
Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesThe concept of age-dependent host control of cancer development raises the natural question of how these effects manifest across the host tissue/organ types with which a tumor interacts, one important component of which is the aging immune system. To investigate this, changes in the spleen, an immune nexus in the mouse, was examined for its age-dependent interactive influence on the carcinogenesis process. The model is the C57BL/6 male mice (adolescent, young adult, middle-aged, and old or 68, 143, 551 and 736 days old respectively) with and without a syngeneic murine tumor implant. Through global transcriptome analysis, immune-related functions were found to be key regulators in the spleen associated with tumor progression as a function of age with CD2, CD3, CCL19, and CCL5 being the key molecules involved. Surprisingly, other than CCL5, all key factors and immune-related functions were not active in spleens from non-tumor bearing old mice. Our findings of age-dependent tumor-spleen signaling interaction suggest the existence of a global role of the aging host in carcinogenesis. Suggested is a new avenue for therapeutic improvement that capitalizes on the pervasive role of host aging in dictating the course of this disease.
Tumor-host signaling interaction reveals a systemic, age-dependent splenic immune influence on tumor development.
Age, Specimen part, Disease, Disease stage
View SamplesGene expression, histone modification, DNA methylation, and DNA hydroxymethylation from normal, cirrhotic, and HCC livers Overall design: 10 total samples (2 normal, 4 cirrhosis, 4 HCC). Cirrhosis and HCC are from the same four patients.
Integrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma.
No sample metadata fields
View SamplesGene expression profiles of WT (wild type) and CCM-1, -2, and -3 KD (knockdown of krit1, ccm2 and pdcd10 genes) cells under 2D (Matrigel-coated plastic) and 3D (Matrigel) conditions. Deep sequencing of RNA was performed for cells at the initial (2hrs) and later (6hrs) stages of EC tubule formation. Overall design: Comparative analysis of gene expression of healthy and diseased cells in the tube formation assay
Biomechanics of Endothelial Tubule Formation Differentially Modulated by Cerebral Cavernous Malformation Proteins.
Cell line, Subject
View SamplesOur aim was to identify genes that were differentially expressed in microglia stimulated with Lipopolysaccharide, Luteolin, or both.
Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype.
No sample metadata fields
View SamplesDnmt3a catalyzes DNA methylation of gDNA, which contributes to the transriptional regulations of genes and genomic stability.
Methylation-independent repression of Dnmt3b contributes to oncogenic activity of Dnmt3a in mouse MYC-induced T-cell lymphomagenesis.
Age, Specimen part
View SamplesOur data demonstrated that Bcl6 directly binds and represses trafficking receptors S1pr1 and Grp183 by recruiting Hdac2 through the RD2 domain. Deregulation of these genes impairs B-cell migration and may contribute to the Germinal Center failure in Bcl6RD2MUT mice. Overall design: RNAseq was performed in endogenous BCL6-depleted OCI-LY1 cells rescued with either WT or RD mutant BCL6 (N=3 for each group).
The BCL6 RD2 domain governs commitment of activated B cells to form germinal centers.
No sample metadata fields
View SamplesPreparation of exosomes isolated from semen contain a substantial amount of RNA, mostly from 20 to 100 nucleotides in length. We sequenced separately 20-40 and 40-100 nucleotide fractions of RNA from exosomes isolated from semenal fluid from six healthy donors. We found various classes of small non-coding RNA, including mature microRNA and piwi-RNA, as well as abundant Y RNAs and tRNAs present in both full length and fragmented forms. Specific RNAs were consistently present in all donors. For example, fifteen (of ~2,600 known) microRNAs constituted over 80% of mature microRNA in SE. Additionally, tRNA fragments were strongly enriched for 5’-ends of 18-19 or 30-34 nucleotides in length. Overall design: Size-fractionated small RNA profiles from exosomes isolated from the seminal fluid of six healthy donors
Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions.
No sample metadata fields
View SamplesGene expression changes in the murine colon were determined at early and late stages following colonoscopic-guided pinch biopsy by comparing normal mucosa of sham treated mice to wound beds Overall design: RNA seq analysis was carried out on colonic mucosa of mice 1 hour, 6 hours, 3 days or 6 days in normal tissue following sham treatment or the wound bed following pinch biopsy
Colonoscopic-Guided Pinch Biopsies in Mice as a Useful Model for Evaluating the Roles of Host and Luminal Factors in Colonic Inflammation.
Specimen part, Cell line, Subject
View Samples