Transient expression of two factors, or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference.
Transcriptional signature and memory retention of human-induced pluripotent stem cells.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A Long Noncoding RNA Regulates Sister Chromatid Cohesion.
Cell line
View SamplesLong 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.
A Long Noncoding RNA Regulates Sister Chromatid Cohesion.
Cell line
View SamplesDespite widespread knowledge that bone marrow-resident breast cancer cells (BMRCs) affect tumor progression, signaling mechanisms of BMRCs implicated in maintaining long-term dormancy have not been characterized. To overcome these hurdles, we developed a novel experimental model of tumor dormancy employing circulating tumor cells (CTCs) derived from metastatic breast cancer patients (de novo CTCs), transplanted them in immunocompromised mice, and re-isolated these cells from xenografted mice bone marrow (ex vivo BMRCs) and blood (ex vivo CTCs) to perform downstream transcriptomic analyses.
Molecular Interplay between Dormant Bone Marrow-Resident Cells (BMRCs) and CTCs in Breast Cancer.
Sex, Specimen part, Disease stage
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Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature.
Cell line, Treatment
View SamplesWe report the application of high-throughput sequencing to performed the p53 regulated trancriptome in HCT116 colon cancer cells treated with the DNA damage 5FU. To study the direct targets of p53 we performed ChIP-seq to deterrmined the p53 biding sites and associated with the expression levels. With this study we identified the new genomic regions regulated by p53 and with special attention in those regions that are significally expressed by DNA damage and and are non- coding.
Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature.
Cell line, Treatment
View SamplesProgressive failure of insulin-producing beta cells is the central event leading to diabetes, yet the signalling networks controlling beta cell fate remain poorly understood. Here we show that SRp55, a splicing factor regulated by the diabetes susceptibility gene GLIS3, has a major role in maintaining function and survival of human beta cells. RNA-seq analysis revealed that SRp55 regulates the splicing of genes involved in cell survival and death, insulin secretion and JNK signalling. Specifically, SRp55-mediated splicing changes modulate the function of the pro-apoptotic proteins BIM and BAX, JNK signalling and endoplasmic reticulum stress, explaining why SRp55 depletion triggers beta cell apoptosis. Furthermore, SRp55 depletion inhibits beta cell mitochondrial function, explaining the observed decrease in insulin release. These data unveil a novel layer of regulation of human beta cell function and survival, namely alternative splicing modulated by key splicing regulators such as SRp55 that may crosstalk with candidate genes for diabetes. Overall design: Five independent preparations of EndoC-ßH1 cells exposed to control (siCTL) or SRp55 (siSR#2) siRNAs
SRp55 Regulates a Splicing Network That Controls Human Pancreatic β-Cell Function and Survival.
Treatment, Subject
View SamplesL1 retrotransposons are active elements in the genome, capable of mobilization in neuronal progenitor cells. Previously, we showed that chromatin remodeling during neuronal differentiation allows for a transient stimulation of L1 transcription. The activity of L1 retrotransposons during brain development can impact gene expression and neuronal function. Here we show that L1 neuronal retrotransposition in rodents is increased in the absence of MeCP2, a protein involved in global methylation and human neurodevelopmental diseases. Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that Rett syndrome patients, with MeCP2 mutations, have increased susceptibility for L1 retrotransposition. Our data demonstrate that disease-related genetic mutations can influence the frequency of neuronal L1 retrotransposition, thereby increasing brain-specific genetic mosaicism.
A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells.
Sex, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2.
Specimen part, Disease, Cell line, Treatment, Subject
View SamplesIt has been recently shown that the transcription factor p53 induces the expression of multiple lincRNAs. However, relatively little is known about the role that lincRNAs play in this pathway. Here we characterize a lincRNA named PINT (p53 Induced Noncoding Transcript). We show that PINT is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells, PINT promotes cell proliferation and survival by regulating the expression of genes of TGF-beta, MAPK and p53 pathways. PINT is a nuclear lincRNA that directly interacts with Polycomb Repressive Complex 2 (PRC2), being required for PRC2 targeting of specific genes for repression. Furthermore, PINT functional activity is dependent on PRC2 expression, representing a connection between the p53 pathway and epigenetic regulation by PRC2. We have also identified PINT human ortholog (hPINT), which presents suggestive analogies with the mouse lincRNA. hPINT is similarly regulated by p53, and its expression correlates significantly with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, hPINT is significantly downregulated in colon cancer, representing a novel tumor suppressor candidate. Our results not only help our understanding of the role of p53 and lincRNAs in cancer, but also contribute to the open debate regarding the utility of mouse models for the study of lincRNAs.
Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2.
Specimen part, Treatment
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