PPARs Regulate The Differentiation Of Mouse Embryonic Stem Cells Into Insulin-Producing Cells

Embryonic stem (ES) cells are derived from the inner cell mass, which has potential of self-replication and multi-differentiation. They could be differentiated into multiple cell organism, such as neuron cells, cardiomyocyte, hepatocytes. In vitro, its fate is dual determined by the inherent and extracellular microenvironment. However, the ratio of spontaneous differentiation of ES cells into insulin-producing (IP) cells is relatively low. The regulation of micro-environment is expected to promote their differentiation. Recently, researchers pay more attentions in the methods of IP cells biogenesis, and neglect the importance of the elements involved in the differentiation process.Peroxisome proliferator-activated receptor (peroxisome proliferator -activated receptors, PPARs) is a nuclear receptor superfamily and haveα,β,γthree isotypes. It plays an important role in regulation of fat storage and energy catabolism. The function of insulin secretion is closely related with the ATP-biogenesis, and mitochondria are important organelles to produce ATP, which are also regulated by PPARs. PPARαand PPARβhad been found seperately enhances cardiomyogenesis, hepatogenesis and mitochondriogenesis. But little is known whether the PPAR isoforms play an even important role in the process of ES cells into IP cells, which is differentiated from the endoderm cell like hepatocytes, and whether PPARs expression occur with the energy system and secretory function biogenesis. This research aimed to establish a three-step protocol to differentiate ES cells into IP cells, and explore the role of PPARs in this differentiation system. It will provide an experimental basis for the future and the related factors of energy in IP cells biogenesis process, promote renewable drug discovery, explore new drug targets cell therapy and regenerative medicine.