Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Microarray data for rejuvenation experiments through reprogramming

ABSTRACT: Proliferative and replicative senescent fibroblasts from aged human donors were reprogrammed towards pluripotency and re-differentiated in fibroblasts and then further analyzed for rejuvenation assessment. Comparison of microarrays were performed by non hierarchical clustering visualized in with Treeview software

ORGANISM(S): Homo sapiens

SUBMITTER: Jean-Marc Lemaitre

PROVIDER: E-GEOD-27924 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state.

Lapasset Laure L Milhavet Ollivier O Prieur Alexandre A Besnard Emilie E Babled Amelie A Aït-Hamou Nafissa N Leschik Julia J Pellestor Franck F Ramirez Jean-Marie JM De Vos John J Lehmann Sylvain S Lemaitre Jean-Marc JM

Genes & development 20111101 21

Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which contributes to aging and restricted longevity, has been described as a barrier to the derivation of iPSCs. Here we demonstrate, using an optimized protocol, that cellular senescence ...[more]

PMID: 22056670

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Project description:Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of iPSCs to model DS phenotypes, as a prototypical complex human disease, we generated bona-fide DS and wild-type (WT) non-viral iPSCs by episomal reprogramming. DS iPSCs selectively overexpressed chromosome 21 genes, consistent with gene dosage, which was associated with deregulation of thousands of genes throughout the genome. DS and WT iPSCs were neurally converted at >95% efficiency, and had remarkably similar lineage potency, differentiation kinetics, proliferation and axon extension at early time points. However, at later time points DS cultures showed a two-fold bias towards glial lineages. Moreover, DS neural cultures were up to two times more sensitive to oxidative stress induced apoptosis, and this could be prevented by the anti-oxidant N-acetylcysteine. Our results reveal a striking complexity in the genetic alterations caused by trisomy-21 that are likely to underlie DS developmental phenotypes, and indicate a central role for defective early glial development in establishing developmental defects in DS brains. Furthermore, oxidative stress sensitivity is likely to contribute to the accelerated neurodegeneration seen in DS, and we provide proof of concept for screening corrective therapeutics using DS iPSCs and their derivatives. Non-viral DS iPSCs can therefore recapitulate features of complex human disease in vitro, and provide a renewable and ethically unencumbered discovery platform. Control (WT) and Down Syndrome iPSC lines were generated via episomal reprogramming of human donor fibroblasts. Two iPSC clones conforming to iPS criteria (determined by immunocytochemistry detection of pluripotency markers) were developed from each fibroblast donor. Two control (WT) and DS lines each were further characterized and underwent neural differentiation. Multiple biological replicates of donor fibroblast and iPSC from both control (WT) and DS lines, including 3 euploid DS samples and 3 MEL1 hESC controls (total 54 samples) were hybridized to Illumina HT-12 v4 microarray for gene expression analysis.

Project description:The development of reduced-risk products is aimed at providing adult smokers, who are unable to quit, with alternatives to cigarettes that present less risk of harm and smoking-related disease. The use of flavors in the development of these reduced-risk products fulfils an important role in product acceptance. While most flavors are also used by the food industry and are considered safe when ingested, their impact when inhaled is still debated. To overcome this research gap, we developed a three-step approach combining real-time cellular analysis, phenotypic high-content screening assays and gene expression analysis. As a case study, a list of 28 flavors, commonly used in e-liquid formulation, were selected and dissolved individually or as a mixture in a Base Solution composed of propylene glycol, vegetable glycol, and 0.6% nicotine. Various dilutions of these mixtures were assessed in normal human bronchial epithelial cells. Using a real-time impedance-based assay, a Tox-Score corresponding to the ratio of the Base Solution EC50 over flavored solution EC50 was determined for each tested e-liquid. We complemented the e-liquid evaluation by computing a Phenotypic-Score that recapitulates the exposure effects measured using a battery of high-content screening endpoints. Using a systems toxicology approach, we also identified and quantified perturbed molecular pathways impacted specifically by the Base Solution or by the 28-flavor mixture. To conclude, employing a three-pillar based approaches to investigate the effects of flavored solutions in vitro, we were in a position to identify individual flavors that appeared to have the potential to contribute greatly to the overall mixture effect (citronellol and alpha-pinene). Finally, by assessing modified mixtures we showed that, although cytotoxic effect where found when assessed individually, alpha-pinene was not contributing to the overall mixture cytotoxicity. Most of the cytotoxic effect appeared to mainly derive by the presence of citronellol and remaining flavors were still contributing due to synergistic effects.

Dataset Information

Microarray data for rejuvenation experiments through reprogramming

Publications

Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state.

Similar Datasets

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