MicroRNAs (miRNAs) are small RNAs that play important regulatory roles in many cellular pathways. MiRNAs associate with members of the Argonaute (Ago) protein family and bind to partially complementary sequences on mRNAs and induce translational repression or mRNA decay. MiRNA expression can be controlled by transcription factors and can therefore be cell type- or tissue-specific. Here we have analyzed miRNA expression profiles in murine monocyte-derived dendritic cells (DCs) and macrophages upon stimulation with LPS, LDL, eLDL and oxLDL to identify not only stimuli-specific miRNA, but also to identify a hierarchical miRNA system involving miR-155. For this, miR-155 knockout dendritic cells and macrophages were also sequenced using the same stimuli. Overall design: Sequencing of murine monocyte-derived dendritic cells and macrophages (each wild type and miR-155 knock out cells) matured and stimulated, respectively, by LPS, oxLDL, eLDL or LDL.
A miR-155-dependent microRNA hierarchy in dendritic cell maturation and macrophage activation.
Specimen part, Cell line, Subject
View SamplesmicroRNAs (miRNAs) are small non-coding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3’ untranslated region (UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer-independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1-3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected. Overall design: Examination of miRNAs associated with endogenous human Ago1-4 in HeLa cells
microRNAs associated with the different human Argonaute proteins.
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View SamplesExon expression profiling was performed on 37 clinical DLBCL samples and subsequently analyzed using alternative splice analysis of vairance (asANOVA) implemented in Partek Genomics Suite in order to identify alternative spliced genes.
Expression of NOTCH3 exon 16 differentiates Diffuse Large B-cell Lymphoma into molecular subtypes and is associated with prognosis.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
General detoxification and stress responses are mediated by oxidized lipids through TGA transcription factors in Arabidopsis.
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View SamplesThe specific ablation of Rb1 gene in epidermis (RbF/F;K14cre) promotes proliferation and altered differentiation but does not produce spontaneous tumour development. These phenotypic changes are associated with increased expression of E2F members and E2F-dependent transcriptional activity. Here, we have focused on the possible dependence on E2F1 gene function. We have generated mice that lack Rb1 in epidermis in an inducible manner (RbF/F;K14creERTM). These mice are indistinguishable from those lacking pRb in this tissue in a constitutive manner (RbF/F;K14cre). In an E2F1-null background (RbF/F;K14creERTM; E2F1-/- mice), the phenotype due to acute Rb1 loss is not ameliorated by E2F1 loss, but rather exacerbated, indicating that pRb functions in epidermis do not rely solely on E2F1. On the other hand, RbF/F;K14creERTM;E2F1-/- mice develope spontaneous epidermal tumours of hair follicle origin with high incidence. These tumours, which retain a functional p19arf/p53 axis, also show aberrant activation of catenin/Wnt pathway. Gene expression studies revealed that these tumours display relevant similarities with specific human tumours. These data demonstrate that the Rb/E2F1 axis exerts essential functions not only in maintaining epidermal homeostasis, but also in suppressing tumour development in epidermis, and that the disruption of this pathway may induce tumour progression through specific alteration of developmental programs.
E2F1 loss induces spontaneous tumour development in Rb-deficient epidermis.
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View Samples12-oxo-phytodienoic acid (OPDA) and phytoprostane A1 (PPA1) are cyclopentenone oxylipins that are formed via the enzymatic
General detoxification and stress responses are mediated by oxidized lipids through TGA transcription factors in Arabidopsis.
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View SamplesPlant hypocotyls elongate in response to darkness. The response to darkness is gated by the circadian clock, such that wild-type plants (Col) only respond to darkness with growth once every 24 hours, whereas arrhythmic lines, such as CCA1-34, will respond to darkness with growth at any time of day. The experiment here was designed to find genes whose expression was correlated with growth. It should also pick up other genes that are gated by the circadian clock or that are direct targets of CCA1.
Rhythmic growth explained by coincidence between internal and external cues.
Age, Specimen part
View Samples12-Oxo-phytodienoic acid (OPDA) and several phytoprostanes are structurally related cyclopentenone oxylipins that can be formed via the enzymatic jasmonate pathway and a non-enzymatic, free radical-catalyzed pathway, respectively. To elucidate the biological activities of phytoprostanes in comparison to OPDA as well as the metabolism we performed genome-wide expression analysis.
General detoxification and stress responses are mediated by oxidized lipids through TGA transcription factors in Arabidopsis.
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View SamplesAnalysis of protein tyrosine phosphatase 1B (PTP1B) deficient mammary glands from nulliparous mice at estrous and pregnancy day 3, 7, 10 and 15. We used a genetically ablated PTP1B mouse model to gain a deeper knowledge of the role PTP1B plays in mammary gland development and to define the mechanism regulated by this phosphatase.
Protein tyrosine phosphatase 1B restrains mammary alveologenesis and secretory differentiation.
Specimen part
View SamplesThe specific ablation of Rb1 gene in stratified epithelia (RbF/F;K14cre) promotes proliferation and altered differentiation but is insufficient to produce spontaneous tumors. The pRb relative, p107, compensates some of the functions of pRb in these tissues, however RbF/F;K14cre;p107-/- mice die postnatally. Acute pRb loss in stratified epithelia, using an inducible mouse model (RbF/F;K14creERTM), shows that p107 exerts specific tumor suppressor functions in its absence. After simultaneous absence of pRb and p107, p53 transcriptional function is impaired and Pten expression is reduced. All mutant mice develop spontaneous squamous tumors carcinomas rapidly. Gene expression analysis of mouse tumors, besides supporting the impaired p53 function and the susceptibility to Akt/mTOR inhibitors, also revealed significant overlap with human squamous carcinomas. Thus, RbF/F;K14creERTM;p107-/- may constitute a new mouse model for these malignancies. Collectively, these data demonstrate the existence of a previously unreported functional connection between pRb, Pten and p53 tumor suppressors, through p107, of a particular relevance in squamous tumor development.
A novel tumor suppressor network in squamous malignancies.
Specimen part
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