Metabolomics analysis of stem cells and differentiated cells points to chemical unsaturation as a key feature of stem cell metabolites. Manipulation of these metabolites' concentrations directly influences stem cell behavior, highlighting biological oxidation as a driver for differentiation. Metabolites offer an important unexplored complementary approach to understanding the pluripotency of stem cells. Using MS-based metabolomics, we show that embryonic stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. By monitoring the reduced and oxidized glutathione ratio as well as ascorbic acid levels, we demonstrate that the stem cell redox status is regulated during differentiation. On the basis of the oxidative biochemistry of the unsaturated metabolites, we experimentally manipulated specific pathways in embryonic stem cells while monitoring the effects on differentiation. Inhibition of the eicosanoid signaling pathway promoted pluripotency and maintained levels of unsaturated fatty acids. In contrast, downstream oxidized metabolites (for example, neuroprotectin D1) and substrates of pro-oxidative reactions (for example, acyl-carnitines), promoted neuronal and cardiac differentiation. We postulate that the highly unsaturated metabolome sustained by stem cells allows them to differentiate in response to in vivo oxidative processes such as inflammation.
Cyclodepsipeptides comprise a wide variety of cyclic peptides of natural origin and are characterized by the occurrence of at least one ester linkage. The great interest that this class of natural products has elicited in scientific community is explained by their wide range of biological activities, intriguing mechanisms of action and attractive molecular architecture. For example, they display a variety of biological effects, such as immunosuppressant, antibiotic, antifungi, antiinflammatory or antitumoral activities. In addition, many of these cyclic depsipeptides represent useful tools for the research of biological processes involved in cellular regulation. The present review deals with the most interesting aspects of the biology and the chemistry of some of these compounds.
Aggregation-Induced Emission (AIE) in organic molecules has recently attracted the attention of the scientific community because of their potential applications in different fields. Compared to small molecules, little attention has been paid to polymers and oligomers that exhibit AIE, despite having excellent properties such as high emission efficiency in aggregate and solid states, signal amplification effect, good processability and the availability of multiple functionalization sites. In addition to these features, if the molecular structure is fully conjugated, intramolecular electronic interactions between the composing chromophores may appear, thus giving rise to a wealth of new photophysical properties. In this review, we focus on selected fully conjugated oligomers, dendrimers and polymers, and briefly summarize their synthetic routes, fluorescence properties and potential applications. An exhaustive comparison between spectroscopic results in solution and aggregates or in solid state has been collected in almost all examples, and an opinion on the future direction of the field is briefly stated.
14 January 2011 in Angewandte Chemie International Edition