We here show that loss of imprinting (LOI) of IGF2 is a frequent and early event in the development of colon cancer and occurs throughout the large intestine. LOI leads to AKT1-dependent activation and suppression of a defined set of genes, many of which are cell cycle related. Our results further showed that IGF2 induces non-canonical wnt signaling. We hypothesize that IGF2 and Wnt5a cooperate in cancer progression. LOI is an attractive target for tumor prevention or targeted therapy.
Carcinoma of the colon and rectum with deregulation of insulin-like growth factor 2 signaling: clinical and molecular implications.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition.
Specimen part, Treatment
View SamplesTreatment of leukemia cells with 1,25-dihydroxyvitamin D3 may overcome their differentiation block and lead to the transition from myeloblasts to monocytes. To identify microRNA-mRNA networks relevant for myeloid differentiation, we profiled the expression of mRNAs and microRNAs associated to the low- and high-density ribosomal fractions in leukemic cells and in their differentiated monocytic counterpart. Intersection between mRNAs shifted across the fractions after treatment with putative target genes of modulated microRNAs showed a series of molecular networks relevant for the monocyte cell fate determination
Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition.
Specimen part, Treatment
View SamplesThe p90 ribosomal S6 kinase (RSK) family, a downstream target of Ras/extracellular signal-regulated kinase (ERK) signaling, can mediate cross-talk with the mammalian target of rapamycin complex 1 (mTORC1) pathway. As RSK connects two oncogenic pathways in gliomas, we investigated the protein levels of the RSK isoforms RSK1-4 in non-tumoral brain (NB) and grade I-IV gliomas. RSK4 expression was not detected in any brain tissues, whereas RSK3 expression was very low, with GBMs demonstrating the lowest RSK3 protein levels. When compared to NB or low-grade gliomas (LGG), a group of glioblastomas (RSK1hi) that excluded long-survivor cases expressed higher levels of RSK1. No difference was observed in RSK2 median-expression levels among NB and gliomas; however, high levels of RSK2 in glioblastomas (GBM) were associated with worse survival. RSK1hi and, to a lesser extent, RSK2hi GBMs, showed higher levels of phosphorylated RSK, which indicates RSK activation. Transcriptome analysis indicated that most RSK1hi GBMs belonged to the mesenchymal subtype, and RSK1 expression strongly correlated with gene expression signature of immune infiltrates, in particular of activated-natural killer cells and M2 macrophages. In an independent cohort, we confirmed that RSK1hi GBMs exclude long-survivors, and RSK1 expression was associated with high protein levels of the mesenchymal subtype marker LAPTM5, as well as with high expression of CD68, which indicated the presence of infiltrating immune cells. An RSK1 signature was obtained based on differentially expressed mRNAs and validated in public glioma datasets. Enrichment of RSK1 signature followed glioma progression, recapitulating RSK1 protein expression, and was associated with worse survival not only in GBM but also in LGG. In conclusion, both RSK1 and RSK2 associate with glioma malignity, but displaying isoform-specific peculiarities. The progression-dependent expression and association with immune infiltration, suggests RSK1 as a potential progression marker and therapeutic target for gliomas.
Aberrant expression of RSK1 characterizes high-grade gliomas with immune infiltration.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcription-dependent generation of a specialized chromatin structure at the TCRβ locus.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination.
No sample metadata fields
View SamplesWe profiled gene expression from a stratified cohort of subjects to define influenza vaccine response in Young and Old
Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination.
No sample metadata fields
View SamplesRecent studies have revealed a myriad of non-coding transcripts in different organisms. For instances, the presence of short bidirectional transcripts is a hallmark of active promoters in mammals, while upstream non-coding transcripts can be detected at most expressed genes in conditions where the RNA degradation machinery is inhibited. Here, we used RNA-seq with very high sequencing depth to characterize strand specific transcripts from primary mouse tissues. We found that a substantial fraction of gene promoters sustain expression of long non-coding antisense transcripts. These transcripts have an average size of 6 kb, have features of mature transcripts, but remain associated with the chromatin. We named this new class of non-coding RNAs Long Upstream Antisense Transcripts (LUAT). Strikingly, the LUAT and coding gene pairs are usually co-regulated, with the associated genes often/generally coding for transcriptional regulators functioning during development and cell differentiation. Indeed, these bidirectional promoters share several characteristic of developmental gene promoters, including large CpG islands and high degree of conservation, and display symetrical GC skews. Finally, we found that bidirectional promoters have enlarged platforms of Pol II initiation, associated with an intensified rate of early transcriptional elongation. We concluded that promoters of developmental regulators are characterized by a specialized mechanism of Pol II transcription, whereby Pol II poising is directly coupled to relaxed bidirectional transcription. Overall design: Expression of noncoding RNA transcripts in CD4-,CD8- double negative thymocytes from Rag2-/- mice was studied by strand-specific, ribosomal-depleted RNA-seq experiment, using Illumina sequencer
Divergent transcription is associated with promoters of transcriptional regulators.
Specimen part, Cell line, Subject
View SamplesThe classification of neurons into distinct types is an ongoing effort aimed at revealing and understanding the diversity of the components of the nervous system. Recently available methods allow us to determine the gene expression pattern of individual neurons in the mammalian cerebral cortex to generate powerful categorization schemes. For a thorough understanding of neuronal diversity such genetic categorization schemes need to be combined with traditional classification parameters like position, axonal projection or response properties to sensory stimulation. Here we describe a method to link the gene expression of individual neurons with their position, axonal projection or sensory response properties. Neurons are labeled in vivo based on their anatomical or functional properties and, using patch clamp pipettes, their RNA individually harvested in vitro for RNAseq. With this method we can determine the genetic expression pattern of functionally and anatomically identified individual neurons. Overall design: single cortical neurons were patch clamped and the RNA harvested; single neuron mRNA profiles were generated by deep sequencing
Correlating Anatomy and Function with Gene Expression in Individual Neurons by Combining <i>in Vivo</i> Labeling, Patch Clamp, and Single Cell RNA-seq.
Cell line, Subject
View SamplesBacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of the genotoxins as effectors during the course of acute and chronic infections remains poorly characterized.To address this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine chronic infections. Immunocompetent mice were chronically infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium) strains, encoding either a functional (MC71-TT) or an inactive (MC71-DcdtB) typhoid toxin.
The Typhoid Toxin Promotes Host Survival and the Establishment of a Persistent Asymptomatic Infection.
No sample metadata fields
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