Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into several distinct lineages including adipocytes and osteoblasts. Differentiation requires sophisticate coordination between genetic and epigenetic processes. Multipotent stem cell contains lots of key maternally inherited transcriptional factors to maintain the pluripotency including Oct3/4 and Sox2, as well as epigenetic factors for histone modifications such as Polycomb group (PcG) protein EZH2 and Eed, proteins of histone metabolism (Padi4), and chromatin remodelers. Furthermore, the differentiation of adipogenic and osteogenic lineages exists mutually exclusive. Disruption of the balance between MSC osteoblast and adipocyte differentiation is associated with various human diseases. Many enzymes and transcriptional factors are known to involve in adipocyte and osteobalst differentiation, but the causative molecular events in the regulation of the differentiation between adipocytes and osteoblasts still remain unclear. Hence, in an attempt to pursue these issues, the following approaches are proposed: (1) To examine the involvement of protein kinases/signaling pathways such as MAPK and Receptor Tyrosine Kinase (RTK) families in MSCs adipogenesis and osteogenesis; (2) To identify novel proteins involved in differentiation of MSCs into adipocytes and osteoblasts and further explore their roles in differentiation; (3) To elucidate the regulatory mechanism of Polycomb EZH2 methyltransferase in differentiation of MSCs into adipocytes and osteoblasts. Success of this study will provide fundamental knowledge to understand signal network for stem cell biology and may pave a way for future cell-based therapy.
