Project description:The naive embryonic stem cells (nESCs) display unique characteristics mirroring naive pluripotency in vivo, but the molecular mechanisms underlying the self-renewal of nESCs remain incompletely understood. Here we analyzed stranded transcriptomes in mouse nESCs and epiblast-like cells (EpiLCs), and identified 135 long non-coding RNAs (lncRNAs) preferentially expressed in nESCs. We further investigated the functions of Lncenc1, a highly abundant lncRNA in mouse nESCs. Knockdown or knockout of Lncenc1 in mouse nESCs leads to significantly decreased expression of core pluripotency genes and significant reduction of colony formation capability. Furthermore, depletion of Lncenc1 down-regulates the glycolysis pathway, as indicated by significant decreases of glycolysis genes expression, glucose consumption, lactate production and Seahorse data. Mechanically, Lncenc1 associates with RNA-binding proteins PTBP1 and HNRNPK functionally. Together, we demonstrate that Lncenc1 regulates the glycolysis in mouse nESCs, suggesting novel functions of lncRNAs in linking energy metabolism and pluripotent stem cells.
Project description:The naive embryonic stem cells (nESCs) display unique characteristics mirroring naive pluripotency in vivo, but the molecular mechanisms underlying the self-renewal of nESCs remain incompletely understood. Here we analyzed stranded transcriptomes in mouse nESCs and epiblast-like cells (EpiLCs), and identified 135 long non-coding RNAs (lncRNAs) preferentially expressed in nESCs. We further investigated the functions of Lncenc1, a highly abundant lncRNA in mouse nESCs. Knockdown or knockout of Lncenc1 in mouse nESCs leads to significantly decreased expression of core pluripotency genes and significant reduction of colony formation capability. Furthermore, depletion of Lncenc1 down-regulates the glycolysis pathway, as indicated by significant decreases of glycolysis genes expression, glucose consumption, lactate production and Seahorse data. Mechanically, Lncenc1 associates with RNA-binding proteins PTBP1 and HNRNPK functionally. Together, we demonstrate that Lncenc1 regulates the glycolysis in mouse nESCs, suggesting novel functions of lncRNAs in linking energy metabolism and pluripotent stem cells.
Project description:Here we propose a set of molecular criteria for evaluating the naive human pluripotent state. We show by RNA-seq that transcription of transposable elements provides a sensitive measure of the concordance between pluripotent stem cells and early human development. RNA-seq of 4 naive ES samples in 4i/LA, 3 naive ES samples in 5i/LA, 2 transgene-dependant naive ES cell samples, and 5 primed ES cell samples (in hESM)
Project description:1. Evaluate the diagnostic value of long noncoding RNA (CCAT1) expression by RT-PCR in peripheral blood in colorectal cancer patients versus normal healthy control personal.
2. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in diagnosis of colorectal cancer patients & its relation to tumor staging.
3. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in precancerous colorectal diseases.
4. Compare long noncoding RNA (CCAT1) expression with traditional marker; carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9) in diagnosis of colorectal cancer.
Project description:Here we propose a set of molecular criteria for evaluating the naive human pluripotent state. We show by RNA-seq that transcription of transposable elements provides a sensitive measure of the concordance between pluripotent stem cells and early human development. RNA-seq of 3 naive ES samples in NHSM (Gafni et al.) and 3 primed ES cell samples (in hESM)
Project description:We employed whole-genome RNA-sequencing to profile mRNAs and both annotated and novel long noncoding RNAs (lncRNAs) in human naive, central memory, and effector memory CD4+ T cells. Loci transcribing both lineage-specific annotated and novel lncRNA are adjacent to lineage-specific protein-coding genes in the genome. Lineage-specific novel lncRNA loci are transcribed from lineage-specific typical- and supertranscriptional enhancers and are not multiexonic, thus are more similar to enhancer RNAs. Novel enhancer-associated lncRNAs transcribed from the IFNG locus bind the transcription factor NF-κB and enhance binding of NF-κB to the IFNG genomic locus. Depletion of the annotated lncRNA, IFNG-AS1, or one IFNG enhancer-associated lncRNA abrogates IFNG expression by memory T cells, indicating these lncRNAs have biologic function.
Project description:Long noncoding RNAs (lncRNAs) have appeared to be involved in the most diverse cellular processes through multiple mechanisms. Here we describe a previously uncharacterized human lncRNA, CONCR (cohesion regulator noncoding RNA), transcriptionally activated by MYC, which is upregulated in multiple cancer types. The expression of CONCR is cell cycle-regulated, and it is required for cell cycle progression and DNA replication. Moreover, cells depleted of CONCR show severe defects in sister chromatid cohesion, suggesting an essential role for CONCR in cohesion establishment during cell division. CONCR interacts with and regulates the activity of DDX11, a DNA-dependent ATPase and helicase involved in DNA replication. These findings suggest a novel mechanism of action for CONCR in the modulation of DDX11 enzymatic activity, unveiling the direct involvement of a lncRNA in the establishment of sister chromatid cohesion. Characterization of the function of the long noncoding RNA CONCR. A549 were transfected with a control siRNA or with a combination of two siRNAs targeting CONCR. Three independent siRNA-mediated knockdowns (siRNA CONCR REP1, 2 and 3) and controls (siRNA Control REP1, 2 and 3) were used for the analysis.