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Student Number 983204031
Author Jia-an Wu(吳家安)
Author's Email Address No Public.
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Department Chemical and Materials Engineering
Year 2011
Semester 1
Degree Master
Type of Document Master's Thesis
Language zh-TW.Big5 Chinese
Title Elucidate the signaling pathway of PDMCs (Placenta-Derived Multipotent Cells) differentiated into Neuron-like cells.
Date of Defense 2012-01-06
Page Count 90
Keyword
  • neural differentiation
  • PDMC
  • signal transduction
  • Abstract In recent years, the research of regenerative medicine focus on the studying and utilizing stem cells. Current sources of stem cells include embryonic stem cells (ESCs) and adult stem cells (ASCs). However, there are numerous ethical concerns exist in ESCs and as to ASCs, which usually obtained from the bone marrow through an invasive procedure. The placenta-derived multipotent cells (PDMCs) are an ethically uncontroversial source, and the cells exhibit the ability to differentiate into many cellular types, including osteoblasts, adipocytes, hepatocytes, and neurons. Therefore, PDMCs could be the considerable alternative resources of mesenchymal stem cell.
    It has been found that under 3-isobutyl-1-methylxanthine (IBMX) inductions, the PDMCs were capable of differentiating into neural-like cells; however, the signal transduction scenario and molecular mechanism behind the phenomenon are still unknown, therefore, we attempts to study this process by phosphoproteomic approaches. After phosphoprotein enrichment with IMAC from IBMX induced PDMCs, two dimensional gel electrophoresis following LC/MS-MS identification were enrolled and the phosphorylated proteins specific induced by IBMX were identified and analyzed by the signal transduction database tool.
    After Western blot validation and literature searches, we found that IBMX would induce phosphorylation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK), and c-Jun and their sequential phosphorylation might involve in the signal transduction in the neural cell differentiation. Besides, cell morphology changes would also be induced through dephosphorylation of other proteins such as Heat Shock Protein 27 (HSP27). However, the phosphorylation regulations and their physiological roles need to be further validated. The information provide by this thesis may help us decipher the mechanism of neuron differentiation and may contribute to the neural degenerative disease treatment in the future.
    Table of Content 摘要 i
    Abstract iii
    誌謝 v
    目錄 vii
    圖目錄 ix
    表目錄 ix
    第一章 緒論 1
    第二章 文獻回顧 2
    2.1 幹細胞 2
    2.1.1 幹細胞研究背景 2
    2.1.2 何謂幹細胞 3
    2.1.3 幹細胞的分類 4
    2.1.4 幹細胞的來源 5
    2.1.5胎盤源多功能細胞(placenta-derived multipotent cells,PDMCs) 7
    2.1.6 胎盤源多功能細胞的神經誘導分化 8
    2.2 細胞訊息傳遞 9
    2.2.1 細胞訊息傳遞系統的基本特徵 10
    2.2.2 神經幹細胞分化成神經寡突細胞之訊息傳導路徑 11
    2.3 磷酸化蛋白質體學 14
    2.3.1 蛋白質體學 (Proteomics) 14
    2.3.2 磷酸化蛋白質介紹 16
    2.3.3 磷酸化分子純化 19
    2.3.3.1 免疫沉降法 20
    2.3.3.2 親和純化法 21
    2.3.3.3化學修飾法 24
    2.3.4 質譜分析 24
    2.4 研究目的 25
    第三章 材料與方法 26
    3.1 實驗設備 26
    3.2 實驗藥品 27
    3.3 實驗方法 29
    3.3.1 細胞培養技術 29
    3.3.2 免疫組織化學染色(Immunohistochemistry,IHC) 31
    3.3.2 蛋白質定量分析 32
    3.3.3 磷酸化蛋白純化 33
    3.3.4 二維膠體電泳法 (two-dimensional electrophoresis; 2-DE) 34
    3.3.5 蛋白質膠內酵素水解(In-gel digestion) 39
    3.3.6 蛋白質溶液內酵素水解(In-solution digestion) 40
    3.3.7 蛋白質身分鑑定 40
    3.3.8 西方墨點分析法(Western Blotting Analysis) 41
    第四章 結果與討論 45
    4.1 細胞型態的觀察及免疫組織化學染色(IHC) 45
    4.2 磷酸化蛋白的純化 46
    4.3 二維膠體電泳分析 48
    4.3.1 純化後的磷酸化蛋白於二維膠體電泳分佈 48
    4.3.2 不同誘導時間經IMAC純化磷酸化蛋白後的二維電泳膠圖 49
    4.3.3 二維膠體電泳結果分析 53
    4.4 西方墨電法驗證 56
    4.5 添加PKC及ERK的抑制劑測試結果 60
    4.6 推測可能的訊息傳導途徑: 66
    4.6.1 PKC/ERK/c-Jun66
    4.6.2 HSP27/cytoskeleton protein 68
    第五章 結論與建議 70
    參考文獻 72
    附錄 液相層析串聯式質譜(LC-MS/MS)與SwissProt資料庫比對結果 80
    附錄 溶液內酵素水解結果比對KEGG MAPK pathway圖 88
    附錄 與ERK1與ERK2具有交互作用之基因差異89
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    Date of Submission 2012-01-18

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