人體胚胎幹細胞之次細胞蛋白質體定量分析

以作者查詢圖書館館藏

、以作者查詢臺灣博碩士

、以作者查詢全國書目

、勘誤回報

、線上人數：46

、訪客IP：3.144.123.153

姓名

林春妙(Chung-Miao Lin) 查詢紙本館藏

畢業系所

化學學系

論文名稱

人體胚胎幹細胞之次細胞蛋白質體定量分析
(Quantitative Analysis of Subcellular Proteome of Human Embryonic Stem Cells)

相關論文

★ 以質譜技術探討非共價鍵結蛋白質聚合物之結構	★ 以蛋白質體學探討在大腸桿菌中甲醇利用代謝途徑
★ Data-independent acquisition mass spectrometry analysis for identification of cerebrospinal fluid biomarker of reversible cerebral vasoconstriction syndrome	★ 利用具有親合性標籤的穩定同位素試劑針對蛋白質磷酸化反應程度的定量方法
★ 奈米粒子結合親和質譜術應用於人體血漿的多樣性免疫分析方法	★ 親和質譜術應用於特定蛋白質之變異結構檢視與定量的研究
★ 利用磁性奈米探針與基質輔助雷射脫附/游離飛行時間質譜儀進行人類血液中前列腺特異抗原的定量	★ 親和性質譜術應用在人類血漿檢測與定量氯屈磷酸
★ 運用兩性親水作用層析磁性奈米粒子順序性純化醣基化和磷酸化胜?	★ 開發精簡及迅速的方法應用於深度磷酸化蛋白質體學剖析
★ 磷酸化蛋白體質譜法應用於微量組織

檔案

[Endnote RIS 格式]

[Bibtex 格式]

[相關文章]

[文章引用]

[完整記錄]

[館藏目錄]

[檢視]

[下載]

本電子論文使用權限為同意立即開放。
已達開放權限電子全文僅授權使用者為學術研究之目的，進行個人非營利性質之檢索、閱讀、列印。
請遵守中華民國著作權法之相關規定，切勿任意重製、散佈、改作、轉貼、播送，以免觸法。

摘要(中)

人體的胚胎幹細胞是一種具分化成各種不同細胞類型且同時具有再生能力的多能性細胞(pluripotency)，所以胚胎幹細胞在再生醫學以及開發藥物的應用上有很大的潛力。膜蛋白質已經被發現與調控胚胎幹細胞有關係，可以廣泛地應用在幹細胞的分類和純化或者可以用來監測幹細胞分化的階段。例如:人體胚胎幹細胞的表面蛋白Notch受體，經研究報導指出當Notch受體被活化時，Notch受體被酵素切割後，位於細胞質內的片段會從細胞膜易位到細胞核並且進一步的造成胚胎幹細胞的朝向神經細胞分化。因此，在胚胎幹細胞的細胞膜、細胞質以及細胞核等次細胞蛋白質體進行定量分析，比較胚胎幹細胞分化前後的蛋白質表現亮差異，不僅可以幫助鑑定新的表面蛋白標誌，也可能找到關於調控胚胎幹細胞功能的分子。在此研究上，由於培養胚胎幹細胞並維持胚胎幹細胞的未分化是很困難的，所以在蛋白質體的分析上，我們所能得到的胚胎幹細胞數量是有限的。
為了克服這項限制，此論文發展一個靈敏的定量策略，結合微量樣品的分群方法(fractionation)和蛋白質體的定量分析。目前已發表一項分群技術StageTip (Stop and Go extraction tips)，此技術提供高效率、高回收率以及高重複性的少量樣品分離。我們分析了強陰離子交換與強陽離子交換的StageTip 分群方法，在經由強陽離子交換分離後蛋白質被鑑定的數量從445(沒有分群的結果)增加到765；利用強陰離子交換分離則能將蛋白質數量增加到902個，其中有623 (59.7 %) 蛋白質是強陽離子交換分離與強陰離子交換分離共同能鑑定到的，而強陰離子交換分離能獲得比強陰離子交換分離多出17.9 %的蛋白質數量。接著，我們使用強陰離子交換分離結合等重相對標記絕對定量(iTRAQ)策略並應用在胚胎幹細胞的次細胞蛋白質體分析。結果顯示有6236、4234以及2061個蛋白質在細胞核、細胞質與細胞膜的部分被鑑定到；其中，有3125、1408與865個蛋白質分別在細胞核、細胞質與細胞膜能成功得到分化前後的蛋白質變化量。在具有異常變化量的細胞膜蛋白質中，有部分蛋白質已經有文獻報導過是胚胎幹細胞或分化後的標記分子。除此之外，還有192個表面膜蛋白具有差異表現量，可能是潛在的胚胎幹細胞和分化後的標記分子。我們也觀察到有差異表現的蛋白質會在不同的細胞位置可能發生易位，例如 -catenin 從細胞質易位到細胞核時，可以調控胚胎幹細胞的多能性。因此，我們的策略不僅能幫助發現專一的胚胎幹細胞生物標記，也能勾勒出胚胎幹細胞的再生機制與分化機制。

摘要(英)

Human embryonic stem cells (hESCs) are pluripotent cells that are uniquely capable of differentiation and self-renewal and have a great potential in regenerative medicine and drug discovery. Membrane proteins have been investigated to play important roles in regulating ESC functions and expected to be extensively used for stem cell classification and purification and monitored of the differentiation stages. For example, the NOTCH receptor, a cell surface protein of hESCs, will translocate from membrane to nucleus when it is activated and further differentiated toward the neural fates. As a result, we hypothesize that a comprehensive quantitative analysis of the subcellular proteome, including membrane, cytosolic and nuclear fractions between hESCs and differentiated cells, will help to identify not only new cell surface markers but also molecules involving in regulation of ES functions. However, due to the difficulties in maintenance and culturing of hESCs, very limited cell number can be obtained for proteome analysis.
To overcome this challenge, we aim to develop a sensitive quantitation strategy integrating a micro-fractionation method for quantitative proteomic analysis of the low sample amount of stem cells. StageTips (Stop and Go Extraction Tips) have been reported to provide separation of a few micrograms of sample with high efficiency, recovery and reproducibility. After StageTip fractionation, the number of protein increased from 445 to 765 and 902 by using SCX-StageTip and SAX-StageTip fractionation respectively. In addition, we compared the SAX-StageTip and SCX-StageTip using membrane proteins purified from HeLa cells. A total of 623 proteins (59.7 %) are commonly identified. Regarding the identification number, SAX-StageTip fractionation can obtain 17.9% higher number than SCX-StageTip fractionation. We applied SAX-StageTip fractionation with iTRAQ quantitation strategy on hESC subcellular proteomics. 6236, 4234 and 2061 proteins were identified, of which 3125, 1408 and 865 proteins were successfully quantified in nucleus, cytosol and membrane fraction, respectively. Several differentially expressed proteins had been reported as specific hESC markers and EB markers. In addition, there were 192 differentially expressed plasma membrane proteins which may be considered as potential hESC markers or EB markers. Several differentially expressed proteins would translocate from different cellular localization such as -catenin which have been reported to regulate hESC pluripotency with translocation from cytoplasm into nucleus. Our strategy can not only help to discover the specific marker candidates for hESC but may delineate the mechanism of self-renewal and differentiation.

關鍵字(中)

★ 人體胚胎幹細胞
★ 強陽離子交換
★ 強陰離子交換

關鍵字(英)

★ hESC
★ membrane proteome
★ SAX-StageTip
★ SCX-StageTip

論文目次

中文摘要 i
Abstract iii
謝誌 v
Table of Contents vi
List of Fugure ix
List of Tables xii
Abbreviations xiii
Chapter 1 Introduction 1
1.1 Significance of Membrane Proteins 1
1.2 Peptide Fractionation Approaches for Proteomics 2
1.2.1 Ion-Exchange Chromatography (IEC) 2
1.2.2 Reversed-Phase Liquid Chromatography (RPLC) 3
1.2.3 Recently Advances in Peptide Fractionation Strategies 3
1.3 Quantitative Methods for Membrane Proteomics 4
1.3.1 Stable Isotope Labeling Technology 4
1.4 Introduction of Human Embryonic Stem Cell (hESC) 6
1.5 Protein Trafficking in hESCs 8
1.6 Thesis Objective 8
Chapter 2 Material And Methods 10
2.1 Material 10
2.1.1 Chemical 10
2.2 Cell Culture for Hela Cell 11
2.3 Sample Preparation 11
2.3.1 Membrane Protein Purification 11
2.3.2 Gel-Assisted Digestion 12
2.4 Protein and Peptide Assay 13
2.4.1 Coomassie (Bradford) Protein Assay Kit 13
2.4.2 BCA Protein Assay 13
2.5 Desalting and Concentration 13
2.5.1 ZipTip® Pipette Tips 13
2.5.2 C18-StageTip 14
2.6 Quantitative Proteomic Analysis by iTRAQ Labeling 14
2.6.1 iTRAQ Labeling Reaction with Four Stages of Peptides 14
2.6.2 Peptide Fractionation by Strong Cation Exchange Chromatography 15
2.6.3 SCX-StageTip Fractionation 15
2.6.4 SAX-StageTip Fractionation 16
2.7 RPLC-MS/MS Analysis 16
2.8 Database Search and Protein Identification 17
Chapter 3 Result 18
3.1 Evaluation of Membrane Protein Purity 18
3.2 Develop an Efficient Peptide Fractionation Method for Small Amount of Sample 18
3.2.1 Large-scale Identification of Membrane Proteome by SCX Liquid Chromatography and LC-MS/MS 19
3.2.2 Evaluation of Separation Efficiency of SAX- and SCX-StageTip Fractionation 19
3.2.3 Evaluation of the Sample Amount for SAX StageTip Fractionation 20
3.2.4 Pilot Test of the Quantitative Membrane Proteomics on HeLa Cell by SAX-StageTip fractionation and iTRAQ Labeling 21
3.3 Application on Quantitation of Subcellular Proteome during hESC Differentiation 22
Chapter 4 Discussion 27
4.1 A Sensitive Quantitation Strategy for Comprehensive Membrane Proteome Analysis of Limited hESC Cells 27
4.2 Pathway Mapping of Differentially Expressed Proteins during Human Embryonic Stem Cell Differentiation 27
Chapter 5 Conclusion 30
References 31
Figures 36
Tables 52

參考文獻

(1) Fagerberg, L.; Jonasson, K.; von Heijne, G.; Uhlén, M.; Berglund, L.: "Prediction of the human membrane proteome". PROTEOMICS 2010, 10, 1141-1149.
(2) Cafiso, D. S.: ’Structure and Interactions of C2 Domains at Membrane Surfaces". In Protein–Lipid Interactions; Wiley-VCH Verlag GmbH & Co. KGaA, 2006; pp 403-422.
(3) Shukla, H. D.; Vaitiekunas, P.; Cotter, R. J.: "Advances in membrane proteomics and cancer biomarker discovery: Current status and future perspective". PROTEOMICS 2012, 12, 3085-3104.
(4) Streuli, C. H.: "Integrins and cell-fate determination". Journal of Cell Science 2009, 122, 171-177.
(5) Blonder, J.; Goshe, M. B.; Moore, R. J.; Pasa-Tolic, L.; Masselon, C. D.; Lipton, M. S.; Smith, R. D.: "Enrichment of Integral Membrane Proteins for Proteomic Analysis Using Liquid Chromatography−Tandem Mass Spectrometry". Journal of Proteome Research 2002, 1, 351-360.
(6) Tan, S.; Tan, H. T.; Chung, M. C. M.: "Membrane proteins and membrane proteomics". PROTEOMICS 2008, 8, 3924-3932.
(7) Mirza, S. P.; Halligan, B. D.; Greene, A. S.; Olivier, M.: "Improved method for the analysis of membrane proteins by mass spectrometry". Physiological Genomics 2007, 30, 89-94.
(8) Han, C.-L.; Chien, C.-W.; Chen, W.-C.; Chen, Y.-R.; Wu, C.-P.; Li, H.; Chen, Y.-J.: "A Multiplexed Quantitative Strategy for Membrane Proteomics: Opportunities for Mining Therapeutic Targets for Autosomal Dominant Polycystic Kidney Disease". Molecular & Cellular Proteomics 2008, 7, 1983-1997.
(9) Lu, X.; Zhu, H.: "Tube-Gel Digestion: A Novel Proteomic Approach for High Throughput Analysis of Membrane Proteins". Molecular & Cellular Proteomics 2005, 4, 1948-1958.
(10) Ru, Q. C.; Zhu, L. A.; Katenhusen, R. A.; Silberman, J.; Brzeski, H.; Liebman, M.; Shriver, C. D.: "Exploring human plasma proteome strategies: High efficiency in-solution digestion protocol for multi-dimensional protein identification technology". Journal of Chromatography A 2006, 1111, 175-191.
(11) Imre, T.; Schlosser, G.; Pocsfalvi, G.; Siciliano, R.; Molnár-Szöllősi, É.; Kremmer, T.; Malorni, A.; Vékey, K.: "Glycosylation site analysis of human alpha-1-acid glycoprotein (AGP) by capillary liquid chromatography—electrospray mass spectrometry". Journal of Mass Spectrometry 2005, 40, 1472-1483.
(12) Washburn, M. P.; Wolters, D.; Yates, J. R.: "Large-scale analysis of the yeast proteome by multidimensional protein identification technology". Nat Biotech 2001, 19, 5.
(13) Ly, L.; Wasinger, V. C.: "Protein and peptide fractionation, enrichment and depletion: Tools for the complex proteome". PROTEOMICS 2011, 11, 513-534.
(14) Gao, M.; Deng, C.; Yu, W.; Zhang, Y.; Yang, P.; Zhang, X.: "Large scale depletion of the high-abundance proteins and analysis of middle- and low-abundance proteins in human liver proteome by multidimensional liquid chromatography". PROTEOMICS 2008, 8, 939-947.
(15) Righetti, P. G.; Castagna, A.; Herbert, B.; Reymond, F.; Rossier, J. S.: "Prefractionation techniques in proteome analysis". PROTEOMICS 2003, 3, 1397-1407.
(16) Rappsilber, J.; Ishihama, Y.; Mann, M.: "Stop and Go Extraction Tips for Matrix-Assisted Laser Desorption/Ionization, Nanoelectrospray, and LC/MS Sample Pretreatment in Proteomics". Analytical Chemistry 2002, 75, 663-670.
(17) Wiśniewski, J. R.; Zougman, A.; Mann, M.: "Combination of FASP and StageTip-Based Fractionation Allows In-Depth Analysis of the Hippocampal Membrane Proteome". Journal of Proteome Research 2009, 8, 5674-5678.
(18) Weekes, M. P. A., Robin; R. Lill, Jennie; Duncan, ;Simon; Lehner, Paul J.: "Comparative Analysis of Techniques to Purify Plasma Membrane Proteins". Journal of Biomolecular Techniques 2010, 21, 8.
(19) Varaprasad Kolla, P. J., Suzette Moes, Sevgi Tercanli, Olav Lapaire, Mahesh Choolani, Sinuhe Hahn: “Quantitative Proteomics Analysis of Maternal Plasma in Down Syndrome Pregnancies Using Isobaric Tagging Reagent (iTRAQ),”. Journal of Biomedicine and Biotechnology 2010, 2010, 10.
(20) Fenselau, C.: "A review of quantitative methods for proteomic studies". Journal of Chromatography B 2007, 855, 14-20.
(21) Thomson, J. A.; Itskovitz-Eldor, J.; Shapiro, S. S.; Waknitz, M. A.; Swiergiel, J. J.; Marshall, V. S.; Jones, J. M.: "Embryonic Stem Cell Lines Derived from Human Blastocysts". Science 1998, 282, 1145-1147.
(22) Prokhorova, T. A.; Rigbolt, K. T. G.; Johansen, P. T.; Henningsen, J.; Kratchmarova, I.; Kassem, M.; Blagoev, B.: "Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Quantitative Comparison of the Membrane Proteomes of Self-renewing and Differentiating Human Embryonic Stem Cells". Molecular & Cellular Proteomics 2009, 8, 959-970.
(23) Harkness, L.; Christiansen, H.; Nehlin, J.; Barington, T.; Andersen, J. S.; Kassem, M.: "Identification of a membrane proteomic signature for human embryonic stem cells independent of culture conditions". Stem Cell Research 2008, 1, 219-227.
(24) McQuade, L. R.; Schmidt, U.; Pascovici, D.; Stojanov, T.; Baker, M. S.: "Improved Membrane Proteomics Coverage of Human Embryonic Stem Cells by Peptide IPG-IEF". Journal of Proteome Research 2009, 8, 5642-5649.
(25) Gerwe, B. A.; Angel, P. M.; West, F. D.; Hasneen, K.; Young, A.; Orlando, R.; Stice, S. L.: "Membrane proteomic signatures of karyotypically normal and abnormal human embryonic stem cell lines and derivatives". PROTEOMICS 2011, 11, 2515-2527.
(26) Sarkar, P.; Collier, T. S.; Randall, S. M.; Muddiman, D. C.; Rao, B. M.: "The subcellular proteome of undifferentiated human embryonic stem cells". PROTEOMICS 2012, 12, 421-430.
(27) Ding, V. M. Y.; Ling, L.; Natarajan, S.; Yap, M. G. S.; Cool, S. M.; Choo, A. B. H.: "FGF-2 modulates Wnt signaling in undifferentiated hESC and iPS cells through activated PI3-K/GSK3β signaling". Journal of Cellular Physiology 2010, 225, 417-428.
(28) Bray, S. J.: "Notch signalling: a simple pathway becomes complex". Nat Rev Mol Cell Biol 2006, 7, 11.
(29) Dreesen, O.; Brivanlou, A.: "Signaling Pathways in Cancer and Embryonic Stem Cells". Stem Cell Rev 2007, 3, 7-17.
(30) Lowell, S.; Benchoua, A.; Heavey, B.; Smith, A. G.: "Notch Promotes Neural Lineage Entry by Pluripotent Embryonic Stem Cells". PLoS Biol 2006, 4, e121.
(31) Munz, M.; Baeuerle, P. A.; Gires, O.: "The Emerging Role of EpCAM in Cancer and Stem Cell Signaling". Cancer Research 2009, 69, 5627-5629.
(32) Peng, J.; Elias, J. E.; Thoreen, C. C.; Licklider, L. J.; Gygi, S. P.: "Evaluation of Multidimensional Chromatography Coupled with Tandem Mass Spectrometry (LC/LC−MS/MS) for Large-Scale Protein Analysis: The Yeast Proteome". Journal of Proteome Research 2002, 2, 43-50.
(33) Slebos, R. J. C.; Brock, J. W. C.; Winters, N. F.; Stuart, S. R.; Martinez, M. A.; Li, M.; Chambers, M. C.; Zimmerman, L. J.; Ham, A. J.; Tabb, D. L.; Liebler, D. C.: "Evaluation of Strong Cation Exchange versus Isoelectric Focusing of Peptides for Multidimensional Liquid Chromatography-Tandem Mass Spectrometry". Journal of Proteome Research 2008, 7, 5286-5294.
(34) Ishihama, Y.; Rappsilber, J.; Mann, M.: "Modular Stop and Go Extraction Tips with Stacked Disks for Parallel and Multidimensional Peptide Fractionation in Proteomics". Journal of Proteome Research 2006, 5, 988-994.
(35) Rappsilber, J.; Mann, M.; Ishihama, Y.: "Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips". Nature Protocols 2007, 2, 1986-1906.
(36) Lin, W.-T.; Hung, W.-N.; Yian, Y.-H.; Wu, K.-P.; Han, C.-L.; Chen, Y.-R.; Chen, Y.-J.; Sung, T.-Y.; Hsu, W.-L.: "Multi-Q: A Fully Automated Tool for Multiplexed Protein Quantitation". Journal of Proteome Research 2006, 5, 2328-2338.
(37) Hsin-Nan, L.; Ching-Tai, C.; Ting-Yi, S.; Shinn-Ying, H.; Wen-Lian, H.: "Protein subcellular localization prediction of eukaryotes using a knowledge-based approach". BMC Bioinformatics 2009, 10.
(38) Yu, C.-S.; Chen, Y.-C.; Lu, C.-H.; Hwang, J.-K.: "Prediction of protein subcellular localization". Proteins: Structure, Function, and Bioinformatics 2006, 64, 643-651.
(39) Laurila, K.; Vihinen, M.: "Prediction of disease-related mutations affecting protein localization". BMC Genomics 2009, 10, 122.
(40) Horton, P.; Park, K.-j.; Obayashi, T.; Nakai, K.: "Protein Subcellular Localisation Prediction with WoLF PSORT". In Asia-Pacific Bioinformatics Conference, 2006; pp 39-48.
(41) Krogh, A.; Larsson, B.; von Heijne, G.; Sonnhammer, E. L. L.: "Predicting transmembrane protein topology with a hidden markov model: application to complete genomes". Journal of Molecular Biology 2001, 305, 567-580.
(42) Lo, A.; Chiu, H.-S.; Sung, T.-Y.; Lyu, P.-C.; Hsu, W.-L.: "Enhanced Membrane Protein Topology Prediction Using a Hierarchical Classification Method and a New Scoring Function". Journal of Proteome Research 2007, 7, 487-496.
(43) Käll, L.; Krogh, A.; Sonnhammer, E. L. L.: "A Combined Transmembrane Topology and Signal Peptide Prediction Method". Journal of Molecular Biology 2004, 338, 1027-1036.
(44) Bernsel, A.; Viklund, H.; Falk, J.; Lindahl, E.; von Heijne, G.; Elofsson, A.: "Prediction of membrane-protein topology from first principles". Proceedings of the National Academy of Sciences 2008, 105, 7177-7181.
(45) Mishra, S.; Ande, S. R.; Nyomba, B. L. G.: "The role of prohibitin in cell signaling". FEBS Journal 2010, 277, 3937-3946.
(46) JIANLI GUO, L. H., PING YUAN, PENG WANG, YANJUN LU, FANGLI TONG,; YU WANG, Y. Y., JUN TIAN and JUN SUN: "ADAM10 overexpression in human non-small cell lung cancer correlates with cell migration and invasion through the activation of the Notch1 signaling pathway". ONCOLOGY REPORTS 2012, 28, 10.
(47) Liu, J.; Sato, C.; Cerletti, M.; Wagers, A.: "Chapter Twelve - Notch Signaling in the Regulation of Stem Cell Self-Renewal and Differentiation". In Current Topics in Developmental Biology; Raphael, K., Ed.; Academic Press, 2010; Vol. Volume 92; pp 367-409.
(48) Ekins, S.; Nikolsky, Y.; Bugrim, A.; Kirillov, E.; Nikolskaya, T.: "Pathway Mapping Tools for Analysis of High Content Data". In High Content Screening; Taylor, D. L., Haskins, J., Giuliano, K., Eds.; Humana Press, 2006; Vol. 356; pp 319-350.
(49) Dormeyer, W.; van Hoof, D.; Braam, S. R.; Heck, A. J. R.; Mummery, C. L.; Krijgsveld, J.: "Plasma Membrane Proteomics of Human Embryonic Stem Cells and Human Embryonal Carcinoma Cells". Journal of Proteome Research 2008, 7, 2936-2951.
(50) Martino, M. M.; Mochizuki, M.; Rothenfluh, D. A.; Rempel, S. A.; Hubbell, J. A.; Barker, T. H.: "Controlling integrin specificity and stem cell differentiation in 2D and 3D environments through regulation of fibronectin domain stability". Biomaterials 2009, 30, 1089-1097.
(51) Su, L.; Lv, X.; Xu, J.; Yin, D.; Zhang, H.; Li, Y.; Zhao, J.; Zhang, S.; Miao, J.: "Neural stem cell differentiation is mediated by integrin β4 in vitro". The International Journal of Biochemistry & Cell Biology 2009, 41, 916-924.
(52) Yamada, K. M.; Even-Ram, S.: "Integrin regulation of growth factor receptors". Nat Cell Biol 2002, 4, 2.
(53) Mitra, S. K.; Hanson, D. A.; Schlaepfer, D. D.: "Focal adhesion kinase: in command and control of cell motility". Nat Rev Mol Cell Biol 2005, 6, 5.
(54) Salasznyk, R. M.; Klees, R. F.; Boskey, A.; Plopper, G. E.: "Activation of FAK is necessary for the osteogenic differentiation of human mesenchymal stem cells on laminin-5". Journal of Cellular Biochemistry 2007, 100, 499-514.
(55) Cofre, J.; Menezes, J. R.; Pizzatti, L.; Abdelhay, E.: "Knock-down of Kaiso induces proliferation and blocks granulocytic differentiation in blast crisis of chronic myeloid leukemia". Cancer Cell International 2012, 12, 28.
(56) Chuang, N. N.; Huang, C. C.: "Interaction of integrin beta1 with cytokeratin 1 in neuroblastoma NMB7 cells". Biochemical Society transactions 2007, 35, 1292-1294.
(57) Kinehara, M.; Kawamura, S.; Tateyama, D.; Suga, M.; Matsumura, H.; Mimura, S.; Hirayama, N.; Hirata, M.; Uchio-Yamada, K.; Kohara, A.; Yanagihara, K.; Furue, M. K.: "Protein Kinase C Regulates Human Pluripotent Stem Cell Self-Renewal". PLoS ONE 2013, 8, e54122.

指導教授

陳玉如(Yu-Ju Chen)

審核日期

2013-7-29

推文