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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/10893


    Title: EZH2 Regulates Neuronal Differentiation of Human Mesenchymal Stem Cells through PIP5K1C-Dependent Calcium Signaling
    Authors: Ling-Tzu Chen
    Contributors: Department of Biotechnology
    Keywords: hMSCs;EZH2;PIP5K1C;neuronal differentiation
    Date: 2010
    Issue Date: 2010-11-08 09:10:44 (UTC+8)
    Publisher: Asia University
    Abstract: Enhancer of zeste homolog 2 (EZH2), a polycomb group (PcG) protein, regulates stem cells renewal and differentiation. Phosphatidylinositol-4-phosphate 5-kinase, type I gamma (PIP5K1C) plays an important role in synthesis of phosphatidylinositol 4, 5-bisphosphate [PI(4,5)P2]. Phospholipase C (PLC) hydrolyzes PI(4,5)P2 into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), in which IP3 is an intracellular messenger to activate calcium signaling. Change in intracellular calcium concentration is required and critical in neuronal differentiation. However, whether EZH2 modulates intracellular calcium signaling and how it regulates neuronal differentiation of human mesenchymal stem cells (hMSCs) are still unclear. In the present study, we successfully induce hMSCs to differentiate into neuronal lineage by detecting the expression of neuronal markers. Knockdown of EZH2 dramatically increases the level of intracellular calcium by 14-fold, and also evokes the expression of PIP5K1C. EZH2 binds the promoter of PIP5K1C in hMSCs and then dissociates after neuronal differentiation. Knockdown of PIP5K1C significantly reduces intracellular calcium release in EZH2-silenced cells, and disrupts neuronal differentiation of hMSCs, indicating that EZH2 regulates intracellular calcium through PIP5K1C, and thus affects neuronal differentiation of hMSCs. Here, we provide the first evidence to show in proliferating hMSCs, EZH2 negatively regulates intracellular calcium. After induction of neuronal differentiation, EZH2 departs from the promoter of PIP5K1C, activates its expression, and evokes intracellular calcium signaling, leading to differentiate hMSCs into neuronal lineages.
    Appears in Collections:[生物科技學系] 博碩士論文

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