Identification of microRNAs - GEN-AU Identification of microRNAs targeting early human adipogenesis

The dramatic increase of overweight and obesity has reached globally the status of the epidemic of the 21st century. Over the last decade, the prevalence of obesity in Western and Westernizing countries has more than doubled, and the increasing incidence of obesity in developing countries as well as of child obesity is alarming. Globally, more than 1 billion adults overweight (BMI > 25) - at least 300 million of them clinically obese (BMI > 30) - cause tremendous costs for our health care systems. The development of obesity is influenced by a combination of environmental factors and inherited genetic predispositions. On the cellular level, obesity is characterized by the excess of adipose tissue. Adipocytes, the principal component of fat tissue, derive from adult mesenchymal stem cells and undergo a multi-stage differentiation called adiopogenesis in order to become mature adipocytes. The identification of protein-coding genes that are involved in the regulation of fat cell (adipocyte) development has greatly increased our knowledge of the mechanisms that underlie this condition. But still, we are far from a complete picture of molecular events in adipocyte differentiation. Especially, the early stage of adipocyte differentiation is not well understood also due to a lack of appropriate cell models. Recently, a novel class of tiny regulators - called microRNAs - has been identified to be involved in cellular differentiation which are recruited from the 97% of the human genome that does not encode proteins, but can downregulate the activity of thousands of genes. More than 300 candidates of this novel class of regulators have been identified predicted to regulate more than 10% of all genes. A small number of microRNAs has been associated with diseases, with the potential for many more. This proposed project addresses the identification of microRNA candidates in the early stage of human adipocyte differentiation (adipogenesis). Therefore, the project goals are to develop a method for the highly-parallel identification of expressed candidates of this novel class of regulators based on microarray technology, to elucidate microRNA expression profiles during early human adipogenesis, and to identify dynamically expressed microRNAs during early human adipogenesis and their corresponding target genes identified by microRNA binding motifs within the target transcripts and validated by their reciprocal expression profile. The results obtained will make an important contribution to understanding cellular differentiation mechanisms and the pathogenesis of extremely frequent diseases of civilization, thereby also laying the foundations for possible commercial applications.