幹細胞之訊息途徑及表基因調控-子計畫三: 研究探討間質幹細胞之脂肪細胞與骨骼細胞分化之分子機轉(1/3)

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Title:	幹細胞之訊息途徑及表基因調控-子計畫三: 研究探討間質幹細胞之脂肪細胞與骨骼細胞分化之分子機轉(1/3)
Other Titles:	Adipocyte and Osteoblast Differentiation of Mesenchymal Stem Cells
Authors:	李龍緣(Long-Yuan Li)
Contributors:	醫學院癌症生物學研究所;中國附醫分子醫學中心癌症生物學
Keywords:	間質幹細胞;脂肪與骨骼細胞分化;訊號傳遞路徑;EZH2;Mesenchymal stem cells, adipocyte and osteobalst differentiation, signalpathways, EZH2
Date:	2008-11-30
Issue Date:	2009-09-01 15:57:05 (UTC+8)
Abstract:	人類間質幹細胞具有多重分化成許多不同細胞型態的能力，例如可以分化成脂肪與骨骼細胞。幹細胞分化的過程中是透過複雜的遺傳性(genetic)與基因外修飾(epigenetic) 所共同調控，因而幹細胞保有許多由母系所遺傳下來的轉錄因子(transcription factor) 來保持幹細胞本身的多重分化的特性，例如Oct3/4 與Sox2，以及基因外修飾histone 的 polycomb group 蛋白質，如EZH2 與Eed。間質幹細胞在分化成脂肪與骨骼細胞的過程是相互調控與排斥的，若間質幹細胞分化成脂肪與骨骼細胞之間的調控被破壞，將會引起許多不同的疾病。目前已知有許多酵素與轉錄因子參與於脂肪與骨骼細胞分化的調控，但主要的分子調控機轉並不是很清楚。因此本計畫擬從下列三方面深入探討調控間質幹細胞分化為脂肪與骨骼細胞的分子機轉。(1)利用MAPK 與RTK 家族之抗體矩陣(antibody array)來研究參與調控間質幹細胞分化成脂肪與骨骼細胞的蛋白激酶(Protein Kinase)。(2)利用蛋白質質譜分析(Mass spectrum)來找尋參與脂肪與骨骼細胞分化調控的新蛋白質。(3)利用ChIP-on-ChIP 實驗，探討polycomb EZH2 在調控間質幹細胞分化為脂肪與骨骼細胞的分子機制。本計劃的研究成果不僅可增進我們對於幹細胞訊息傳遞網路的瞭解，並有助於未來發展幹細胞療法。 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.
Appears in Collections:	[Graduate Institute of Cancer Biology] Research reports

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