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 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
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 SamplesThis study investigates three radiation exposure scenarios in BALB/c and C57BL/6 mice: (1) low dose (LD) group -- four weekly doses of 7.5 cGy, (2) high dose (HD) group -- four weekly doses of 1.8 Gy, (3) unexposed group -- four weekly sham exposures. We then used comparative expression profiles of the mouse mammary gland and cardiac blood to build a model of candidate tissue functions associated with LD cancer susceptibility in these strains and murine and human knowledgebases to characterize these tissue functions and their relevance to breast cancer.
Genetic differences in transcript responses to low-dose ionizing radiation identify tissue functions associated with breast cancer susceptibility.
Sex, Age, 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 SamplesWe report RNA Seq analysis using Illumina nextSeq500 of human beta cells EndoC-BH1 treated with FGF2 to induce dedifferentiation. FGF2 treatment induced dedifferentiation of EndoC-BH1 cells. Indeed, we observed a strong decrease in expression of ß-cell markers, (INS, MAFB, SLC2A2, SLC30A8 and GCK). Opposingly, we identifed positive markers of human ß cell dedifferentiation, as attested by increased expression of mature ß-cell disallowed transcription factors (MYC, HES1, SOX9 and NEUROG3). Interestingly, our temporal analysis revealed that loss of expression of ß cell specific markers preceded the induction of ß cell disallowed genes. Overall design: human beta cells EndoC-BH1 were treated with FGF2 (100ng/L) during 4, 24, 72 and 144h. RNA was isolated post treatment, along with the non-treated controls, and RNA Seq was performed using Illumina nextSeq500 to generate a full transcriptome analysis of gene expression during dedifferentiation of pancreatic beta cells.
Modeling human pancreatic beta cell dedifferentiation.
Specimen part, Cell line, Subject, Time
View SamplesWe performed microarray analysis to evaluate differences in the transcriptome of type 2 diabetic human islets compared to non-diabetic islet samples.
Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells.
Sex, Age, Specimen part, Disease, Disease stage
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 SamplesContinuous stress caused by smoking induces changes in the cell population of small airway epithelium, with basal cell hyperplasia and goblet cell metaplasia at the expense of ciliated cells, and there is now compiling evidence that basal cells play a key role in the early pathogenesis of Chronic Obtructive Pulmonary Disease (COPD).
Microarray analysis identifies defects in regenerative and immune response pathways in COPD airway basal cells.
Specimen part, Disease stage
View Samples