Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/90298
標題: Establishment of cell culture systems and induced methods of mouse pluripotent stem cell
建立小鼠多能性細胞培養系統與誘導式多能性幹細胞
作者: Jhe-Syuan Chang
張哲軒
關鍵字: 原核胚顯微注射法;細胞外基質;再程式化;小分子藥物;Microinjection;Extra cellular matrix;Reprogramming;Small molecules
引用: Adams, C. E. 1962. Studies on prenatal mortality in the rabbit, Oryctolagus cuniculus: the effect of transferring varying numbers of eggs. J Endocrinol 24:471-90. Amit, M., C. Shariki, V. Margulets and J. Itskovitz-Eldor. 2004. Feeder layer- and serum-free culture of human embryonic stem cells. Biol Reprod 70:837-45. Auerbach, A. B., R. Norinsky, W. Ho, K. Losos, Q. Guo, S. Chatterjee and A. L. Joyner. 2003. Strain-dependent differences in the efficiency of transgenic mouse production. Transgenic Res 12:59-69. Avilion, A. A., S. K. Nicolis, L. H. Pevny, L. Perez, N. Vivian and R. Lovell-Badge. 2003. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev 17:126-40. Bach, F. H. 1998. Xenotransplantation: problems and prospects. Annu Rev Med 49:301-10. Bain, J., L. Plater, M. Elliott, N. Shpiro, C. J. Hastie, H. McLauchlan, I. Klevernic, J. S. Arthur, D. R. Alessi and P. Cohen. 2007. The selectivity of protein kinase inhibitors: a further update. Biochem J 408:297-315. Bao, S., F. Tang, X. Li, K. Hayashi, A. Gillich, K. Lao and M. A. Surani. 2009. Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells. Nature 461:1292-5. Behringer, R. 2014. Manipulating the mouse embryo : a laboratory manual. Fourth edition. ed. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press. Blondin, P., K. Coenen, L. A. Guilbault and M. A. Sirard. 1996. Superovulation can reduce the developmental competence of bovine embryos. Theriogenology 46:1191-203. Braam, S. R., L. Zeinstra, S. Litjens, D. Ward-van Oostwaard, S. van den Brink, L. van Laake, F. Lebrin, P. Kats, R. Hochstenbach, R. Passier, A. Sonnenberg and C. L. Mummery. 2008. Recombinant vitronectin is a functionally defined substrate that supports human embryonic stem cell self-renewal via alphavbeta5 integrin. Stem Cells 26:2257-65. Bradley, A., M. Evans, M. H. Kaufman and E. Robertson. 1984. Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines. Nature 309:255-6. Brafman, D. A., C. W. Chang, A. Fernandez, K. Willert, S. Varghese and S. Chien. 2010. Long-term human pluripotent stem cell self-renewal on synthetic polymer surfaces. Biomaterials 31:9135-44. Brinster, R. L., J. M. Allen, R. R. Behringer, R. E. Gelinas and R. D. Palmiter. 1988. Introns increase transcriptional efficiency in transgenic mice. Proc Natl Acad Sci U S A 85:836-40. Brinster, R. L., H. Y. Chen, M. E. Trumbauer, M. K. Yagle and R. D. Palmiter. 1985. Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. Proc Natl Acad Sci U S A 82:4438-42. Brons, I. G., L. E. Smithers, M. W. Trotter, P. Rugg-Gunn, B. Sun, S. M. Chuva de Sousa Lopes, S. K. Howlett, A. Clarkson, L. Ahrlund-Richter, R. A. Pedersen and L. Vallier. 2007. Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448:191-5. Buehr, M., S. Meek, K. Blair, J. Yang, J. Ure, J. Silva, R. McLay, J. Hall, Q. L. Ying and A. Smith. 2008. Capture of authentic embryonic stem cells from rat blastocysts. Cell 135:1287-98. Burdon, T. G. and R. J. Wall. 1992. Fate of microinjected genes in preimplantation mouse embryos. Mol Reprod Dev 33:436-42. Carney, E. W. and R. H. Foote. 1990. Effects of superovulation, embryo recovery, culture system and embryo transfer on development of rabbit embryos in vivo and in vitro. J Reprod Fertil 89:543-51. Chazaud, C., Y. Yamanaka, T. Pawson and J. Rossant. 2006. Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway. Dev Cell 10:615-24. Chen C. H., H. W. Wang, Y. L. Chang, C. T. Fan, K. H. Lee and C. K. Chuang. 2013. Generation of mouse induced pluripotent stem cells by transient transfection of plasmid DNA encoding reprogramming factors. J Chin Soc Anim Sci Suppl 43: 212. Chen, G., D. R. Gulbranson, Z. Hou, J. M. Bolin, V. Ruotti, M. D. Probasco, K. Smuga-Otto, S. E. Howden, N. R. Diol, N. E. Propson, R. Wagner, G. O. Lee, J. Antosiewicz-Bourget, J. M. Teng and J. A. Thomson. 2011. Chemically defined conditions for human iPSC derivation and culture. Nat Methods 8:424-9. Chen, T., D. Yuan, B. Wei, J. Jiang, J. Kang, K. Ling, Y. Gu, J. Li, L. Xiao and G. Pei. 2010. E-cadherin-mediated cell-cell contact is critical for induced pluripotent stem cell generation. Stem Cells 28:1315-25. Chen, X., H. Xu, P. Yuan, F. Fang, M. Huss, V. B. Vega, E. Wong, Y. L. Orlov, W. Zhang, J. Jiang, Y. H. Loh, H. C. Yeo, Z. X. Yeo, V. Narang, K. R. Govindarajan, B. Leong, A. Shahab, Y. Ruan, G. Bourque, W. K. Sung, N. D. Clarke, C. L. Wei and H. H. Ng. 2008. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133:1106-17. Cho, H. J., C. S. Lee, Y. W. Kwon, J. S. Paek, S. H. Lee, J. Hur, E. J. Lee, T. Y. Roh, I. S. Chu, S. H. Leem, Y. Kim, H. J. Kang, Y. B. Park and H. S. Kim. 2010. Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation. Blood 116:386-95. Chrenek, P., D. Vasicek, A. V. Makarevich, R. Jurcik, K. Suvegova, V. Parkanyi, M. Bauer, J. Rafay, A. Batorova and R. K. Paleyanda. 2005. Increased transgene integration efficiency upon microinjection of DNA into both pronuclei of rabbit embryos. Transgenic Res 14:417-28. Cloos, P. A., J. Christensen, K. Agger and K. Helin. 2008. Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. Genes Dev 22:1115-40. Cormack, B. P., R. H. Valdivia and S. Falkow. 1996. FACS-optimized mutants of the green fluorescent protein (GFP). Gene 173:33-8. Damak, S., H. Su, N. P. Jay and D. W. Bullock. 1996. Improved wool production in transgenic sheep expressing insulin-like growth factor 1. Biotechnology (N Y) 14:185-8. Dominko, T., M. Mitalipova, B. Haley, Z. Beyhan, E. Memili, B. McKusick and N. L. First. 1999. Bovine oocyte cytoplasm supports development of embryos produced by nuclear transfer of somatic cell nuclei from various mammalian species. Biol Reprod 60:1496-502. Domogatskaya, A., S. Rodin, A. Boutaud and K. Tryggvason. 2008. Laminin-511 but not -332, -111, or -411 enables mouse embryonic stem cell self-renewal in vitro. Stem Cells 26:2800-9. Donnelly, M. L., L. E. Hughes, G. Luke, H. Mendoza, E. ten Dam, D. Gani and M. D. Ryan. 2001. The 'cleavage' activities of foot-and-mouth disease virus 2A site-directed mutants and naturally occurring '2A-like' sequences. J Gen Virol 82:1027-41. Eiselleova, L., I. Peterkova, J. Neradil, I. Slaninova, A. Hampl and P. Dvorak. 2008. Comparative study of mouse and human feeder cells for human embryonic stem cells. Int J Dev Biol 52:353-63. Ellis, J., P. Pasceri, K. C. Tan-Un, X. Wu, A. Harper, P. Fraser and F. Grosveld. 1997. Evaluation of beta-globin gene therapy constructs in single copy transgenic mice. Nucleic Acids Res 25:1296-302. Esteban, M. A., T. Wang, B. Qin, J. Yang, D. Qin, J. Cai, W. Li, Z. Weng, J. Chen, S. Ni, K. Chen, Y. Li, X. Liu, J. Xu, S. Zhang, F. Li, W. He, K. Labuda, Y. Song, A. Peterbauer, S. Wolbank, H. Redl, M. Zhong, D. Cai, L. Zeng and D. Pei. 2010. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 6:71-9. Evans, M. J. and M. H. Kaufman. 1981. Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154-6. Faherty, S., A. Fitzgerald, M. Keohan and L. R. Quinlan. 2007. Self-renewal and differentiation of mouse embryonic stem cells as measured by Oct4 expression: the role of the cAMP/PKA pathway. In Vitro Cell Dev Biol Anim 43:37-47. Forsberg, E. C., D. Bhattacharya and I. L. Weissman. 2006. Hematopoietic stem cells: expression profiling and beyond. Stem Cell Rev 2:23-30. Fowler, R. E. and R. G. Edwards. 1957. Induction of superovulation and pregnancy in mature mice by gonadotrophins. J Endocrinol 15:374-84. Fusaki, N., H. Ban, A. Nishiyama, K. Saeki and M. Hasegawa. 2009. Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proc Jpn Acad Ser B Phys Biol Sci 85:348-62. Gardner, R. L. and R. S. Beddington. 1988. Multi-lineage stem cells in the mammalian embryo. J Cell Sci Suppl 10:11-27. Golovan, S. P., R. G. Meidinger, A. Ajakaiye, M. Cottrill, M. Z. Wiederkehr, D. J. Barney, C. Plante, J. W. Pollard, M. Z. Fan, M. A. Hayes, J. Laursen, J. P. Hjorth, R. R. Hacker, J. P. Phillips and C. W. Forsberg. 2001. Pigs expressing salivary phytase produce low-phosphorus manure. Nat Biotechnol 19:741-5. Gordon, J. W., G. A. Scangos, D. J. Plotkin, J. A. Barbosa and F. H. Ruddle. 1980. Genetic transformation of mouse embryos by microinjection of purified DNA. Proc Natl Acad Sci U S A 77:7380-4. Greenlee, A. R., T. A. Kronenwetter-Koepel, S. J. Kaiser and K. Liu. 2005. Comparison of Matrigel and gelatin substrata for feeder-free culture of undifferentiated mouse embryonic stem cells for toxicity testing. Toxicol In Vitro 19:389-97. Guo, G., J. Yang, J. Nichols, J. S. Hall, I. Eyres, W. Mansfield and A. Smith. 2009. Klf4 reverts developmentally programmed restriction of ground state pluripotency. Development 136:1063-9. Gurskaya, N. G., A. F. Fradkov, N. I. Pounkova, D. B. Staroverov, M. E. Bulina, Y. G. Yanushevich, Y. A. Labas, S. Lukyanov and K. A. Lukyanov. 2003. A colourless green fluorescent protein homologue from the non-fluorescent hydromedusa Aequorea coerulescens and its fluorescent mutants. Biochem J 373:403-8. Hackett, J. A. and M. A. Surani. 2013. DNA methylation dynamics during the mammalian life cycle. Philos Trans R Soc Lond B Biol Sci 368:20110328. Hammer, R. E., R. L. Brinster and R. D. Palmiter. 1985. Use of gene transfer to increase animal growth. Cold Spring Harb Symp Quant Biol 50:379-87. Hammer, R. E., V. G. Pursel, C. E. Rexroad, Jr., R. J. Wall, D. J. Bolt, K. M. Ebert, R. D. Palmiter and R. L. Brinster. 1985. Production of transgenic rabbits, sheep and pigs by microinjection. Nature 315:680-3. Hanna, J., A. W. Cheng, K. Saha, J. Kim, C. J. Lengner, F. Soldner, J. P. Cassady, J. Muffat, B. W. Carey and R. Jaenisch. 2010. Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proc Natl Acad Sci U S A 107:9222-7. Hanna, J. H., K. Saha and R. Jaenisch. 2010. Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues. Cell 143:508-25. Hayashi, Y., M. K. Furue, T. Okamoto, K. Ohnuma, Y. Myoishi, Y. Fukuhara, T. Abe, J. D. Sato, R. Hata and M. Asashima. 2007. Integrins regulate mouse embryonic stem cell self-renewal. Stem Cells 25:3005-15. Hockemeyer, D., F. Soldner, E. G. Cook, Q. Gao, M. Mitalipova and R. Jaenisch. 2008. A drug-inducible system for direct reprogramming of human somatic cells to pluripotency. Cell Stem Cell 3:346-53. Hou, P., Y. Li, X. Zhang, C. Liu, J. Guan, H. Li, T. Zhao, J. Ye, W. Yang, K. Liu, J. Ge, J. Xu, Q. Zhang, Y. Zhao and H. Deng. 2013. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 341:651-4. Huangfu, D., R. Maehr, W. Guo, A. Eijkelenboom, M. Snitow, A. E. Chen and D. A. Melton. 2008. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26:795-7. Huangfu, D., K. Osafune, R. Maehr, W. Guo, A. Eijkelenboom, S. Chen, W. Muhlestein and D. A. Melton. 2008. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol 26:1269-75. Ichida, J. K., J. Blanchard, K. Lam, E. Y. Son, J. E. Chung, D. Egli, K. M. Loh, A. C. Carter, F. P. Di Giorgio, K. Koszka, D. Huangfu, H. Akutsu, D. R. Liu, L. L. Rubin and K. Eggan. 2009. A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell 5:491-503. Ittner, L. M. and J. Gotz. 2007. Pronuclear injection for the production of transgenic mice. Nat Protoc 2:1206-15. Jaenisch, R. and B. Mintz. 1974. Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA. Proc Natl Acad Sci U S A 71:1250-4. Jaenisch, R. and R. Young. 2008. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132:567-82. Jiang, Y., B. N. Jahagirdar, R. L. Reinhardt, R. E. Schwartz, C. D. Keene, X. R. Ortiz-Gonzalez, M. Reyes, T. Lenvik, T. Lund, M. Blackstad, J. Du, S. Aldrich, A. Lisberg, W. C. Low, D. A. Largaespada and C. M. Verfaillie. 2002. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41-9. Judson, R. L., J. E. Babiarz, M. Venere and R. Blelloch. 2009. Embryonic stem cell-specific microRNAs promote induced pluripotency. Nat Biotechnol 27:459-61. Kim, D., C. H. Kim, J. I. Moon, Y. G. Chung, M. Y. Chang, B. S. Han, S. Ko, E. Yang, K. Y. Cha, R. Lanza and K. S. Kim. 2009. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472-6. Kim, M. K., W. R. Wee, C. G. Park and S. J. Kim. 2011. Xenocorneal transplantation. Curr Opin Organ Transplant 16:231-6. Kupriyanov, S., K. Zeh and H. Baribault. 1998. Double pronuclei injection of DNA into zygotes increases yields of transgenic mouse lines. Transgenic Res 7:223-6. Lemmon, M. A. and J. Schlessinger. 2010. Cell signaling by receptor tyrosine kinases. Cell 141:1117-34. Lengner, C. J., A. A. Gimelbrant, J. A. Erwin, A. W. Cheng, M. G. Guenther, G. G. Welstead, R. Alagappan, G. M. Frampton, P. Xu, J. Muffat, S. Santagata, D. Powers, C. B. Barrett, R. A. Young, J. T. Lee, R. Jaenisch and M. Mitalipova. 2010. Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell 141:872-83. Li, L., S. Wang, A. Jezierski, L. Moalim-Nour, K. Mohib, R. J. Parks, S. F. Retta and L. Wang. 2010. A unique interplay between Rap1 and E-cadherin in the endocytic pathway regulates self-renewal of human embryonic stem cells. Stem Cells 28:247-57. Li, R., J. Liang, S. Ni, T. Zhou, X. Qing, H. Li, W. He, J. Chen, F. Li, Q. Zhuang, B. Qin, J. Xu, W. Li, J. Yang, Y. Gan, D. Qin, S. Feng, H. Song, D. Yang, B. Zhang, L. Zeng, L. Lai, M. A. Esteban and D. Pei. 2010. A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell 7:51-63. Li, W., H. Zhou, R. Abujarour, S. Zhu, J. Young Joo, T. Lin, E. Hao, H. R. Scholer, A. Hayek and S. Ding. 2009. Generation of human-induced pluripotent stem cells in the absence of exogenous Sox2. Stem Cells 27:2992-3000. Li, Y., Q. Zhang, X. Yin, W. Yang, Y. Du, P. Hou, J. Ge, C. Liu, W. Zhang, X. Zhang, Y. Wu, H. Li, K. Liu, C. Wu, Z. Song, Y. Zhao, Y. Shi and H. Deng. 2011. Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules. Cell Res 21:196-204. Lin, S. L., D. C. Chang, S. Chang-Lin, C. H. Lin, D. T. Wu, D. T. Chen and S. Y. Ying. 2008. Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state. RNA 14:2115-24. Lin, T., R. Ambasudhan, X. Yuan, W. Li, S. Hilcove, R. Abujarour, X. Lin, H. S. Hahm, E. Hao, A. Hayek and S. Ding. 2009. A chemical platform for improved induction of human iPSCs. Nat Methods 6:805-8. Lu, J., R. Hou, C. J. Booth, S. H. Yang and M. Snyder. 2006. Defined culture conditions of human embryonic stem cells. Proc Natl Acad Sci U S A 103:5688-93. Luo, M., T. Ling, W. Xie, H. Sun, Y. Zhou, Q. Zhu, M. Shen, L. Zong, G. Lyu, Y. Zhao, T. Ye, J. Gu, W. Tao, Z. Lu and I. Grummt. 2013. NuRD blocks reprogramming of mouse somatic cells into pluripotent stem cells. Stem Cells 31:1278-86. Maga, E. A., R. G. Sargent, H. Zeng, S. Pati, D. A. Zarling, S. M. Oppenheim, N. M. Collette, A. L. Moyer, J. S. Conrad-Brink, J. D. Rowe, R. H. BonDurant, G. B. Anderson and J. D. Murray. 2003. Increased efficiency of transgenic livestock production. Transgenic Res 12:485-96. Maherali, N. and K. Hochedlinger. 2009. Tgfbeta signal inhibition cooperates in the induction of iPSCs and replaces Sox2 and cMyc. Curr Biol 19:1718-23. Mali, P., B. K. Chou, J. Yen, Z. Ye, J. Zou, S. Dowey, R. A. Brodsky, J. E. Ohm, W. Yu, S. B. Baylin, K. Yusa, A. Bradley, D. J. Meyers, C. Mukherjee, P. A. Cole and L. Cheng. 2010. Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes. Stem Cells 28:713-20. Marson, A., S. S. Levine, M. F. Cole, G. M. Frampton, T. Brambrink, S. Johnstone, M. G. Guenther, W. K. Johnston, M. Wernig, J. Newman, J. M. Calabrese, L. M. Dennis, T. L. Volkert, S. Gupta, J. Love, N. Hannett, P. A. Sharp, D. P. Bartel, R. Jaenisch and R. A. Young. 2008. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell 134:521-33. Martin, G. R. 1981. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78:7634-8. Martin, M. J., A. Muotri, F. Gage, and A. Varki. 2005. Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med 11 (2):228-32. Maurer, R. R. and R. H. Foote. 1971. Maternal ageing and embryonic mortality in the rabbit. I. Repeated superovulation, embryo culture and transfer. J Reprod Fertil 25:329-41. Maurer, R. R. and R. H. Foote.. 1972. Maternal ageing and embryonic mortality in the rabbit. II. Hormonal changes in young and ageing females. J Reprod Fertil 31:15-22. McKnight, R. A., A. Shamay, L. Sankaran, R. J. Wall and L. Hennighausen. 1992. Matrix-attachment regions can impart position-independent regulation of a tissue-specific gene in transgenic mice. Proc Natl Acad Sci U S A 89:6943-7. McKnight, R. A., M. Spencer, R. J. Wall and L. Hennighausen. 1996. Severe position effects imposed on a 1 kb mouse whey acidic protein gene promoter are overcome by heterologous matrix attachment regions. Mol Reprod Dev 44:179-84. Melkoumian, Z., J. L. Weber, D. M. Weber, A. G. Fadeev, Y. Zhou, P. Dolley-Sonneville, J. Yang, L. Qiu, C. A. Priest, C. Shogbon, A. W. Martin, J. Nelson, P. West, J. P. Beltzer, S. Pal and R. Brandenberger. 2010. Synthetic peptide-acrylate surfaces for long-term self-renewal and cardiomyocyte differentiation of human embryonic stem cells. Nat Biotechnol 28:606-10. Michiue, H., K. Tomizawa, F. Y. Wei, M. Matsushita, Y. F. Lu, T. Ichikawa, T. Tamiya, I. Date and H. Matsui. 2005. The NH2 terminus of influenza virus hemagglutinin-2 subunit peptides enhances the antitumor potency of polyarginine-mediated p53 protein transduction. J Biol Chem 280:8285-9. Mikkelsen, T. S., J. Hanna, X. Zhang, M. Ku, M. Wernig, P. Schorderet, B. E. Bernstein, R. Jaenisch, E. S. Lander and A. Meissner. 2008. Dissecting direct reprogramming through integrative genomic analysis. Nature 454:49-55. Miranda, T. B., C. C. Cortez, C. B. Yoo, G. Liang, M. Abe, T. K. Kelly, V. E. Marquez and P. A. Jones. 2009. DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol Cancer Ther 8:1579-88. Mitsui, K., Y. Tokuzawa, H. Itoh, K. Segawa, M. Murakami, K. Takahashi, M. Maruyama, M. Maeda and S. Yamanaka. 2003. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113:631-42. Miyazaki, T., S. Futaki, K. Hasegawa, M. Kawasaki, N. Sanzen, M. Hayashi, E. Kawase, K. Sekiguchi, N. Nakatsuji and H. Suemori. 2008. Recombinant human laminin isoforms can support the undifferentiated growth of human embryonic stem cells. Biochem Biophys Res Commun 375:27-32. Montoliu, L., A. Schedl, G. Kelsey, P. Lichter, Z. Larin, H. Lehrach and G. Schutz. 1993. Generation of transgenic mice with yeast artificial chromosomes. Cold Spring Harb Symp Quant Biol 58:55-62. Morris, S. A., Y. Guo and M. Zernicka-Goetz. 2012. Developmental plasticity is bound by pluripotency and the Fgf and Wnt signaling pathways. Cell Rep 2:756-65. Muller, M. and G. Brem. 1998. Transgenic approaches to the increase of disease resistance in farm animals. Rev Sci Tech 17:365-78. Muller, M. B. and M. E. Keck. 2002. Genetically engineered mice for studies of stress-related clinical conditions. J Psychiatr Res 36:53-76. Murakami, H., T. Fujimura, K. Nomura and H. Imai. 2002. Factors influencing efficient production of transgenic rabbits. Theriogenology 57:2237-45. Nakamura, T., Y. Arai, H. Umehara, M. Masuhara, T. Kimura, H. Taniguchi, T. Sekimoto, M. Ikawa, Y. Yoneda, M. Okabe, S. Tanaka, K. Shiota and T. Nakano. 2007. PGC7/Stella protects against DNA demethylation in early embryogenesis. Nat Cell Biol 9:64-71. Nakanishi, T., A. Kuroiwa, S. Yamada, A. Isotani, A. Yamashita, A. Tairaka, T. Hayashi, T. Takagi, M. Ikawa, Y. Matsuda and M. Okabe. 2002. FISH analysis of 142 EGFP transgene integration sites into the mouse genome. Genomics 80:564-74. Nichols, J. and A. Smith. 2009. Naive and primed pluripotent states. Cell Stem Cell 4:487-92. Nichols, J., B. Zevnik, K. Anastassiadis, H. Niwa, D. Klewe-Nebenius, I. Chambers, H. Scholer and A. Smith. 1998. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95:379-91. Nottle, M. B., H. Nagashima, P. J. Verma, Z. T. Du, C. G. Grupen, R. J. Ashman and S. MacIlfatrick. 1997. Developments in transgenic techniques in pigs. J Reprod Fertil Suppl 52:237-44. Okabe, M., M. Ikawa, K. Kominami, T. Nakanishi and Y. Nishimune. 1997. 'Green mice' as a source of ubiquitous green cells. FEBS Lett 407:313-9. Okano, H., M. Nakamura, K. Yoshida, Y. Okada, O. Tsuji, S. Nori, E. Ikeda, S. Yamanaka and K. Miura. 2013. Steps toward safe cell therapy using induced pluripotent stem cells. Circ Res 112:523-33. Okano, H. and S. Yamanaka. 2014. iPS cell technologies: significance and applications to CNS regeneration and disease. Mol Brain 7:22. Okita, K., T. Ichisaka and S. Yamanaka. 2007. Generation of germline-competent induced pluripotent stem cells. Nature 448:313-7. Okita, K., M. Nakagawa, H. Hyenjong, T. Ichisaka and S. Yamanaka. 2008. Generation of mouse induced pluripotent stem cells without viral vectors. Science 322:949-53. Palmiter, R. D., H. Y. Chen and R. L. Brinster. 1982. Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring. Cell 29:701-10. Palmiter, R. D., E. P. Sandgren, M. R. Avarbock, D. D. Allen and R. L. Brinster. 1991. Heterologous introns can enhance expression of transgenes in mice. Proc Natl Acad Sci U S A 88:478-82. Pieters, T., and F. van Roy. 2014. Role of cell-cell adhesion complexes in embryonic stem cell biology. J Cell Sci 127 (Pt 12):2603-13. Rais, Y., A. Zviran, S. Geula, O. Gafni, E. Chomsky, S. Viukov, A. A. Mansour, I. Caspi, V. Krupalnik, M. Zerbib, I. Maza, N. Mor, D. Baran, L. Weinberger, D. A. Jaitin, D. Lara-Astiaso, R. Blecher-Gonen, Z. Shipony, Z. Mukamel, T. Hagai, S. Gilad, D. Amann-Zalcenstein, A. Tanay, I. Amit, N. Novershtern and J. H. Hanna. 2013. Deterministic direct reprogramming of somatic cells to pluripotency. Nature 502:65-70. Rosner, M. H., M. A. Vigano, K. Ozato, P. M. Timmons, F. Poirier, P. W. Rigby and L. M. Staudt. 1990. A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature 345:686-92. Rudolph, N. S. 1999. Biopharmaceutical production in transgenic livestock. Trends Biotechnol 17:367-74. Sato, A., E. Otsu, H. Negishi, T. Utsunomiya and T. Arima. 2007. Aberrant DNA methylation of imprinted loci in superovulated oocytes. Hum Reprod 22:26-35. Sato, N., L. Meijer, L. Skaltsounis, P. Greengard and A. H. Brivanlou. 2004. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 10:55-63. Sauer, B. and N. Henderson. 1988. Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc Natl Acad Sci U S A 85:5166-70. Schugar, R. C., P. D. Robbins and B. M. Deasy. 2008. Small molecules in stem cell self-renewal and differentiation. Gene Ther 15:126-35. Shi, Y., C. Desponts, J. T. Do, H. S. Hahm, H. R. Scholer and S. Ding. 2008. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3:568-74. Silva, J., J. Nichols, T. W. Theunissen, G. Guo, A. L. van Oosten, O. Barrandon, J. Wray, S. Yamanaka, I. Chambers and A. Smith. 2009. Nanog is the gateway to the pluripotent ground state. Cell 138:722-37. Silva, S. S., R. K. Rowntree, S. Mekhoubad and J. T. Lee. 2008. X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells. Proc Natl Acad Sci U S A 105:4820-5. Smith, A. G. 2001. Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol 17:435-62. Sommer, C. A., M. Stadtfeld, G. J. Murphy, K. Hochedlinger, D. N. Kotton and G. Mostoslavsky. 2009. Induced pluripotent stem cell generation using a single lentiviral stem cell cassette. Stem Cells 27:543-9. Stadtfeld, M., N. Maherali, D. T. Breault and K. Hochedlinger. 2008. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2:230-40. Stadtfeld, M., M. Nagaya, J. Utikal, G. Weir and K. Hochedlinger. 2008. Induced pluripotent stem cells generated without viral integration. Science 322:945-9. Takahashi, K., M. Narita, M. Yokura, T. Ichisaka and S. Yamanaka. 2009. Human induced pluripotent stem cells on autologous feeders. PLoS One 4:e8067. Takahashi, K. and S. Yamanaka. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-76. Tesar, P. J., J. G. Chenoweth, F. A. Brook, T. J. Davies, E. P. Evans, D. L. Mack, R. L. Gardner and R. D. McKay. 2007. New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448:196-9. Theunissen, T. W., B. E. Powell, H. Wang, M. Mitalipova, D. A. Faddah, J. Reddy, Z. P. Fan, D. Maetzel, K. Ganz, L. Shi, T. Lungjangwa, S. Imsoonthornruksa, Y. Stelzer, S. Rangarajan, A. D'Alessio, J. Zhang, Q. Gao, M. M. Dawlaty, R. A. Young, N. S. Gray and R. Jaenisch. 2014. Systematic identification of culture conditions for induction and maintenance of naive human pluripotency. Cell Stem Cell 15:471-87. Thomson, J. A., J. Itskovitz-Eldor, S. S. Shapiro, M. A. Waknitz, J. J. Swiergiel, V. S. Marshall and J. M. Jones. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282:1145-7. Tseng, Y. L., K. Kuwaki, F. J. Dor, A. Shimizu, S. Houser, Y. Hisashi, K. Yamada, S. C. Robson, M. Awwad, H. J. Schuurman, D. H. Sachs and D. K. Cooper. 2005. alpha1,3-Galactosyltransferase gene-knockout pig heart transplantation in baboons with survival approaching 6 months. Transplantation 80:1493-500. Tsumura, A., T. Hayakawa, Y. Kumaki, S. Takebayashi, M. Sakaue, C. Matsuoka, K. Shimotohno, F. Ishikawa, E. Li, H. R. Ueda, J. Nakayama and M. Okano. 2006. Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Genes Cells 11:805-14. Villa-Diaz, L. G., H. Nandivada, J. Ding, N. C. Nogueira-de-Souza, P. H. Krebsbach, K. S. O'Shea, J. Lahann and G. D. Smith. 2010. Synthetic polymer coatings for long-term growth of human embryonic stem cells. Nat Biotechnol 28:581-3. Wadia, J. S. and S. F. Dowdy. 2002. Protein transduction technology. Curr Opin Biotechnol 13:52-6. Warren, L., P. D. Manos, T. Ahfeldt, Y. H. Loh, H. Li, F. Lau, W. Ebina, P. K. Mandal, Z. D. Smith, A. Meissner, G. Q. Daley, A. S. Brack, J. J. Collins, C. Cowan, T. M. Schlaeger and D. J. Rossi. 2010. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7:618-30. Wang, T., K. Chen, X. Zeng, J. Yang, Y. Wu, X. Shi, B. Qin, L. Zeng, M. A. Esteban, G. Pan and D. Pei. 2011. The histone demethylases Jhdm1a/1b enhance somatic cell reprogramming in a vitamin-C-dependent manner. Cell Stem Cell 9:575-87. Wheeler, M. B., G. T. Bleck and S. M. Donovan. 2001. Transgenic alteration of sow milk to improve piglet growth and health. Reprod Suppl 58:313-24. Wilkie, T. M., R. L. Brinster and R. D. Palmiter. 1986. Germline and somatic mosaicism in transgenic mice. Dev Biol 118:9-18. Williams, R. L., D. J. Hilton, S. Pease, T. A. Willson, C. L. Stewart, D. P. Gearing, E. F. Wagner, D. Metcalf, N. A. Nicola and N. M. Gough. 1988. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 336:684-7. Xu, C., M. S. Inokuma, J. Denham, K. Golds, P. Kundu, J. D. Gold and M. K. Carpenter. 2001. Feeder-free growth of undifferentiated human embryonic stem cells. Nat Biotechnol 19:971-4. Xu, Y., Y. Shi and S. Ding. 2008. A chemical approach to stem-cell biology and regenerative medicine. Nature 453:338-44. Xu, Y., X. Zhu, H. S. Hahm, W. Wei, E. Hao, A. Hayek and S. Ding. 2010. Revealing a core signaling regulatory mechanism for pluripotent stem cell survival and self-renewal by small molecules. Proc Natl Acad Sci U S A 107:8129-34. Yamada, K. M. and S. Even-Ram. 2002. Integrin regulation of growth factor receptors. Nat Cell Biol 4:E75-6. Yeom, Y. I., G. Fuhrmann, C. E. Ovitt, A. Brehm, K. Ohbo, M. Gross, K. Hubner and H. R. Scholer. 1996. Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells. Development 122:881-94. Ying, Q. L., J. Nichols, I. Chambers and A. Smith. 2003. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 115:281-92. Ying, Q. L., J. Wray, J. Nichols, L. Batlle-Morera, B. Doble, J. Woodgett, P. Cohen and A. Smith. 2008. The ground state of embryonic stem cell self-renewal. Nature 453:519-23. Yoshimizu, T., N. Sugiyama, M. De Felice, Y. I. Yeom, K. Ohbo, K. Masuko, M. Obinata, K. Abe, H. R. Scholer and Y. Matsui. 1999. Germline-specific expression of the Oct-4/green fluorescent protein (GFP) transgene in mice. Dev Growth Differ 41:675-84. Zhang, P., R. Andrianakos, Y. Yang, C. Liu and W. Lu. 2010. Kruppel-like factor 4 (Klf4) prevents embryonic stem (ES) cell differentiation by regulating Nanog gene expression. J Biol Chem 285:9180-9. Zhang, Z., X. Lv, Y. Wang, Y. Chen, R. Zheng, H. Sun, G. Bian, Y. Xiao, Q. Li, Q. Yang, J. Ai, J. Duan, R. Tan, Y. Liu, Y. Yang, Y. Wei and Q. Zhou. 2009. Success of murine embryo transfer increased by a modified transfer pipette. J Reprod Dev 55:94-7. Zhao, X. Y., W. Li, Z. Lv, L. Liu, M. Tong, T. Hai, J. Hao, C. L. Guo, Q. W. Ma, L. Wang, F. Zeng and Q. Zhou. 2009. iPS cells produce viable mice through tetraploid complementation. Nature 461:86-90. Zhou, H., S. Wu, J. Y. Joo, S. Zhu, D. W. Han, T. Lin, S. Trauger, G. Bien, S. Yao, Y. Zhu, G. Siuzdak, H. R. Scholer, L. Duan and S. Ding. 2009. Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4:381-4. Zhu, N., H. X. Jia, X. K. Liu, X. E. Zhao, Q. Wei and B. H. Ma. 2012. [Measuring the estrus cycle and its effect on superovulation in mice]. Dongwuxue Yanjiu 33:276-82. Zhu, S., W. Li, H. Zhou, W. Wei, R. Ambasudhan, T. Lin, J. Kim, K. Zhang and S. Ding. 2010. Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell 7:651-5.
摘要: 
於桃莉羊出生前,一般認為哺乳動物細胞的分化為不可逆之生理機制,但自從複製羊桃莉被產製出來後,再經過近20年的努力,目前的研究已發展出數種方式,可將已分化之哺乳動物細胞進行再程式化(reprogramming)。細胞再程式化指的是將已分化之體細胞回復至分化程度較低,或甚至類似幹細胞的狀態。然而,成功將體細胞完全再程式化至「誘發式多能性幹細胞(induced pluripotent stem cells, iPSCs)」的效率仍舊很低。因此,本研究欲藉由不同培養方式與添加物,期能改善細胞再程式化效率。試驗一,為有效辨識小鼠細胞於培養系統或再程式化過程中多能性幹細胞(pluripotent stem cells)之生成,因此構築數個帶有不同Oct4基因啟動子(promoter)序列與綠色螢光蛋白(green fluorescent protein, GFP)報導基因之載體,先以轉染試劑測試外源基因於轉染細胞後之表現能力,挑選符合預期表現之報導基因進行原核顯微注射。產製之Native pOct4-AcGFP (多能性標誌基因) 與pCX-EGFP(對照組)基因轉殖小鼠,經PCR檢測確認其轉殖成功,且均具性腺遺傳能力。觀察不同時期基因轉殖鼠胚之Native pOct4-AcGFP表現模式,為確立所獲得之基因轉殖小鼠可於不同發育期別正確表現報導基因,結果顯示桑椹胚至早期囊胚期鼠胚細胞均具明顯Native pOct4-AcGFP訊號,且隨著胚胎發育pOct4-GFP訊號逐漸聚集於囊胚內細胞團(inner cell mass, ICM)中,隨後僅只表現於胎兒性腺組織,而由Native pOct4-AcGFP基因轉殖小鼠囊胚所建立之胚幹細胞(embryonic stem cells, ESCs)亦具Native pOct4-AcGFP表現能力。此外,此Native pOct4-AcGFP基因轉殖鼠之胎兒成纖維母細胞與尾巴成纖維母細胞等分化細胞則不表現Native pOct4-AcGFP,顯示此載體構築之專一性,適用於後續試驗。試驗二,因無血清(serum free)與無飼養層細胞(feeder free)之培養系統有助於研究多能性幹細胞之生理機制以及未來應用,因此,本試驗將Native pOct4-AcGFP mESCs培養於含不同細胞外基質(extracellular matrices, ECM, 包含Matrigel, StemAdhere, Vitronectin, Gelatin與poly-D-lysine),並以無血清之LIF + 2i(CHIR99021+ PD0325901)培養液進行培養,並分析胚幹細胞之naïve與primed狀態,以及其生長速率與多能性基因之表現。結果顯示,所有試驗組之mESCs均表現Native pOct4-AcGFP,其中培養於poly-D-lysine之mESCs,其生長速度顯著低於其他試驗組(P < 0.01)。利用real-time RT-PCR分析培養於不同ECM上mESCs之naïve, 多能性與較後期primed狀態之標誌基因表現,發現培養於Vitronectin與Gelatin之mESCs mRNA表現圖譜相較於其他處理組接近naïve狀態。以免疫螢光染色法偵測mESCs培養於不同ECM上之Oct4, Sox2, Nanog與Dppa3(naïve marker)以及Gata6(primed marker)之基因表現,發現所有處理組皆表現Dppa3, Oct4, Sox2與Nanog,而無Gata6表現,顯示mESCs於ECM以及LIF + 2i環境下培養可維持其多能性與naïve標誌基因表現。試驗三,以反轉錄病毒(retrovirus)轉染外源性因子Oct4, Sox2, c-myc以及Klf4至體細胞基因組中可使其再程式化為誘發式多能性幹細胞,但病毒基因會嵌入宿主細胞基因組中,可能造成基因組突變與細胞癌化等風險,因此,近年有研究利用非基因嵌入法(non-integrating)使體細胞進行再程式化,但iPSCs產製效率不佳。本試驗以質體短暫性表現外源轉錄因子並搭配小分子藥物進行小鼠胚胎纖維母細胞之再程式化,期望提高非基因嵌入法產製iPSCs之效率。結果顯示,於培養第一週即可出現細胞團(colony),但其結構不易維持在含有血清之培養液,因此,以血清替代物(serum replacement)取代之。而添加小分子藥物Valproic acid sodium salt, CHIR992021, 616452, Tranylcypromine, Forskolin以及3-deazaneplanocin則有助於細胞再程式化,培養至第四週時可獲得大量「pre-iPSCs」。Pre-iPSCs經免疫化學染色檢定確認可表現多能性基因Oct4, Sox2以及Nanog。Pre-iPSCs透過LIF + 2i培養液可篩選出依賴naïve幹細胞訊息調控之iPSCs。總結,雖本試驗之再程式化製程可快速獲得Pre-iPSCs,但未如預期加速於LIF + 2i環境中生成iPSCs之時間,顯示此細胞再程式化製程仍有改善的空間。

It had been believed that the mammalian differentiated cells were unable to return to the undifferentiated status before the birth of Dolly the Sheep. However, after entering the era of post-Dolly, several methods have been developed to reprogram the mammalian differentiated cells during the past two decades. Reprogramming refers to the reversion of somatic cells into a less differentiated state, or even a stem-cell-like state. Nevertheless, to date, reprogramming cells into the fully reprogrammed induced pluripotent stem cells (iPSCs) remains at an inefficient and non-specific process. Hence, the aim of this study was to improve the reprogramming efficiency by using different culture systems and supplementation of small molecules. In Experiment 1, in order to effectively determine the emergence of mouse pluripotent stem cells during cell culture or cellular reprogramming, several reporter vectors, composed of different regulatory regions of Oct4 promoter with green fluorescent protein (GFP) reporter gene, were constructed. These constructs were analyzed for specific expression by using chemical-based transfection into embryonic stem cells (ESCs) or primary cells before conducting pronuclear microinjection to produce transgenic mice. Several transgenic mice carrying native pOct4-AcGFP (a pluripotent reporter) or pCX-GFP (a universal reporter) genes were confirmed by PCR analysis and have been confirmed as germline-transmitted lines. In order to confirm the expression patterns of reporter gene during development in transgenic mice, we collected the in vivo derived transgenic embryos. The native pOct4-AcGFP signals were shown in the cells widely distributed in transgenic embryos at the morula to the early blastocyst stages. Moreover, the native pOct4-AcGFP signals were gradually concentrated into the pluripotent ICM region in the expanded and hatched blastocysts, and then the native pOct4-AcGFP signals were migrated to gonads in fetus. Mouse ESCs derived from pOct4-AcGFP blastocysts also showed intensive GFP signals in the individual cells compared to no expression in the differentiated cell types, such as embryonic and tail-tip fibroblasts. The pOct4-AcGFP mESCs line was ready for the next experiments. In Experiment 2, due to the benefit of serum-free and feeder-free culture systems to the study of the physiological mechanism of pluripotent stem cells and further therapy applications, the aim of this experiment was to analyze the status of naïve and primed, the proliferation rate and the expression of pluripotent gense in the native pOct4-AcGFP mESCs cultured on various extra cellular matrix (ECM) components, including matrigel, stemadhere, vitronectin, gelatin and poly-D-lysine, in the LIF + 2i (CHIR99021+ PD0325901) medium, and without serum and feeder layer. Results showed that native pOct4-AcGFP signals were detected in all treatments. Proliferation of mESCs cultured on that the poly-D-lysine was significantly lower than those in other groups. By real-time RT-PCR, it indicated that the analyzed genes in the native pOct4-AcGFP mESCs cultured on vitronectin expressed in a similar pattern to that cultured on the feeder layer. Additionally, it was found that the naïve marker gene, Dppa3, and the pluripotency marker genes, Oct4, Sox2 and Nanog, were detected in each treatment, while the primed marker gene, GATA6, was undetectable. In conclusion, ESCs cultured on various ECM components with LIF + 2i medium could maintain the expression of pluripotent and and naïve marker genes and proteins. In Experiment 3, previous studies indicated that mature somatic cells can be reprogrammed into a pluripotent state by retrovirus infection of Oct4, Sox2, c-myc and Klf4, or called the Yamanaka factors, which would generate induced pluripotent stem cells (iPSCs). However, retrovirus vectors may induce carcinogenesis or insertional mutagenesis when iPSCs are proliferating. Recently, non-integrating methods were reported to reprogram somatic cells, but the efficiency was low. Hence, the aim of this experiment was to improve the reprogramming efficiency by combining small-molecule compounds, including Valproic acid sodium salt, CHIR99021, 616452, Tranylcypromine, Forskolin and 3-deazaneplanocin, with plasmid transfection of the Yamanaka factors. Results showed that cell colonies appeared at the first week of culture, but the dome shape was unstable when the environment contains serum. Therefore, the culture system was changed into serum-free medium and the pre-iPSCs were generated using serum-free medium combine with small molecules at the fourth week of culture. The pre-iPSCs expressed pluripotent markers Oct4, Sox2 and Nanog protein analyzed by immunocytochemistry (ICC) staining. In conclusion, generated the pre-iPSCs was more efficient in the experiment, but the efficiency of iPSCs generation was not improved largely in LIF + 2i medium and the optimal cell reprogramming conditions for generate iPSCs still require further investigation.
URI: http://hdl.handle.net/11455/90298
Rights: 同意授權瀏覽/列印電子全文服務,2018-08-26起公開。
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