In Vitro and In Vivo Modulation of Alternative Splicing by the Biguanide Metformin.

Major physiological changes are governed by alternative splicing of RNA, and its misregulation may lead to specific diseases. With the use of a genome-wide approach, we show here that this splicing step can be modified by medication and demonstrate the effects of the biguanide metformin, on alternative splicing. The mechanism of action involves AMPK activation and downregulation of the RBM3 RNA-binding protein.

Cytostatic Effect of Repeated Exposure to Simvastatin: A Mechanism for Chronic Myotoxicity Revealed by the Use of Mesodermal Progenitors Derived from Human Pluripotent Stem Cells.

Statin treatment of hypercholesterolemia can lead to chronic myotoxicity which is, in most cases, alleviated by drug withdrawal. Cellular and molecular mechanisms of this adverse effect have been elusive, in particular because of the lack of in vitro models suitable for long-term exposures. We have taken advantage of the properties of human pluripotent stem cell-derived mesodermal precursors, that can be maintained unaltered in vitro for a long period of time, to develop a model of repeated exposures to simvastatin during more than 2 weeks.

Human pluripotent stem cells in drug discovery and predictive toxicology.

Human pluripotent stem cells are a biological resource most commonly considered for their potential in cell therapy or, as it is now called, 'regenerative medicine'. However, in the near future, their most important application for human health may well be totally different, as they are more and more envisioned as opening new routes for pharmacological research. Pluripotent stem cells indeed possess the main attributes that make them theoretically fully equipped for the development of cell-based assays in the fields of drug discovery and predictive toxicology.

[Embryonic stem cells in pharmacology].

Because of their self-renewal and pluripotency properties, human embryonic stem cells (hES) receive a marked attention from scientists and clinicians for regenerative medicine. The most recent application of hES cells may however reside in their use as a tool in drug development. The currently available cellular models for preclinical testing consist in primary and immortalized cells that display limitations in terms of available amount and likeliness to their in vivo counterparts, respectively.

Knockin mice expressing fluorescent delta-opioid receptors uncover G protein-coupled receptor dynamics in vivo.

The combination of fluorescent genetically encoded proteins with mouse engineering provides a fascinating means to study dynamic biological processes in mammals. At present, green fluorescent protein (GFP) mice were mainly developed to study gene expression patterns or cell morphology and migration. Here we used enhanced GFP (EGFP) to achieve functional imaging of a G protein-coupled receptor (GPCR) in vivo.