Direct reprogramming 101

Development Growth and Differentiation

Volumn 52, Issue 3, 2010, Pages 319-333

  Takahashi, Kazutoshi ^a  

^a KYOTO UNIVERSITY   (Japan)

Author keywords

IPS cells; Pluripotecy; Reprogramming

Indexed keywords

KRUPPEL LIKE FACTOR 4; LEUKEMIA INHIBITORY FACTOR; MICRORNA; MYC PROTEIN; OCTAMER TRANSCRIPTION FACTOR 4; PROTEIN P53; RETINOBLASTOMA PROTEIN; STAT3 PROTEIN; TRANSCRIPTION FACTOR NANOG; TRANSCRIPTION FACTOR SOX2;

CELL DIFFERENTIATION; CPG ISLAND; DNA METHYLATION; EMBRYO DEVELOPMENT; EMBRYONIC STEM CELL; EPIGENETICS; GENE EXPRESSION REGULATION; GENE SILENCING; HUMAN; INNER CELL MASS; MOLECULAR INTERACTION; NONHUMAN; NUCLEAR REPROGRAMMING; PLURIPOTENT STEM CELL; REVIEW;

ANIMALS; EMBRYONIC STEM CELLS; EPIGENESIS, GENETIC; GENES, MYC; GENES, TUMOR SUPPRESSOR; HUMANS; KRUPPEL-LIKE TRANSCRIPTION FACTORS; MICE; MICRORNAS; MODELS, BIOLOGICAL; NUCLEAR REPROGRAMMING; NUCLEAR TRANSFER TECHNIQUES; OCTAMER TRANSCRIPTION FACTOR-3; PLURIPOTENT STEM CELLS; SOXB1 TRANSCRIPTION FACTORS;

EID: 77950201396     PISSN: 00121592     EISSN: 1440169X     Source Type: Journal    
DOI: 10.1111/j.1440-169X.2010.01169.x     Document Type: Review

References (172)

1. Aasen, T., Raya, A., Barrero, M. J., Garreta, E., Consiglio, A., Gonzalez, F., Vassena, R., Bilić, J., Pekarik, V., Tiscornia, G., Edel, M., Boué, S. Izpisúa Belmonte, J. C. 2008. Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat. Biotechnol. 26, 1276 1284.
2. Aoi, T., Yae, K., Nakagawa, M., Ichisaka, T., Okita, K., Takahashi, K., Chiba, T. Yamanaka, S. 2008. Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321, 699 702.
3. Avilion, A. A., Nicolis, S. K., Pevny, L. H., Perez, L., Vivian, N. Lovell-Badge, R. 2003. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 17, 126 140.
4. Banito, A., Rashid, S. T., Acosta, J. C., Li, S., Pereira, C. F., Geti, I., Pinho, S., Silva, J. C., Azuara, V., Walsh, M., Vallier, L. Gil, J. 2009. Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev. 23, 2134 2139.
5. Bechard, M. Dalton, S. 2009. Subcellular localization of glycogen synthase kinase 3beta controls embryonic stem cell self-renewal. Mol. Cell. Biol. 29, 2092 2104.
6. Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., Jaenisch, R., Wagschal, A., Feil, R., Schreiber, S. L. Lander, E. S. 2006. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315 326.
7. Bernstein, B. E., Meissner, A. Lander, E. S. 2007. The mammalian epigenome. Cell 128, 669 681.
8. Bhutani, N., Brady, J. J., Damian, M., Sacco, A., Corbel, S. Y. Blau, H. M. 2010. Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature doi:10.1038\nature08752.
9. Boiani, M. Schöler, H. R. 2005. Regulatory networks in embryo-derived pluripotent stem cells. Nat. Rev. Mol. Cell Biol. 6, 872 884.
10. Boland, M. J., Hazen, J. L., Nazor, K. L., Rodriguez, A. R., Gifford, W., Martin, G., Kupriyanov, S. Baldwin, K. K. 2009. Adult mice generated from induced pluripotent stem cells. Nature 461, 91 94.
11. Boyer, L. A., Lee, T. I., Cole, M. F., Johnstone, S. E., Levine, S. S., Zucker, J. P., Guenther, M. G., Kumar, R. M., Murray, H. L., Jenner, R. G., Gifford, D. K., Melton, D. A., Jaenisch, R. Young, R. A. 2005. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947 956.
12. Boyer, L. A., Plath, K., Zeitlinger, J., Brambrink, T., Medeiros, L. A., Lee, T. I., Levine, S. S., Wernig, M., Tajonar, A., Ray, M. K., Otte, A. P., Vidal, M., Gifford, D. K., Young, R. A. Jaenisch, R. 2006. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441, 349 353.
13. Brown, J. P., Wei, W. Sedivy, J. M. 1997. Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 277, 831 834.
14. Byrne, J. A., Pedersen, D. A., Clepper, L. L., Nelson, M., Sanger, W. G., Gokhale, S., Wolf, D. P. Mitalipov, S. M. 2007. Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature 450, 497 502.
15. Card, D. A., Hebbar, P. B., Li, L., Trotter, K. W., Komatsu, Y., Mishina, Y. Archer, T. K. 2008. Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells. Mol. Cell. Biol. 28, 6426 6438.
16. Cartwright, P., McLean, C., Sheppard, A., Rivett, D., Jones, K. Dalton, S. 2005. LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development 132, 885 896.
17. Chambers, I., Colby, D., Robertson, M., Nichols, J., Lee, S., Tweedie, S. Smith, A. 2003. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113, 643 655.
18. Chan, K. K., Zhang, J., Chia, N. Y., Chan, Y. S., Sim, H. S., Tan, K. S., Oh, S. K., Ng, H. H. Choo, A. B. 2009. KLF4 and PBX1 directly regulate NANOG expression in human embryonic stem cells. Stem Cells 27, 2114 2125.
19. Chung, Y., Klimanskaya, I., Becker, S., Marh, J., Lu, S. J., Johnson, J., Meisner, L. Lanza, R. 2006. Embryonic and extraembryonic stem cell lines derived from single mouse blastomeres. Nature 439, 216 219.
20. Chung, Y., Klimanskaya, I., Becker, S., Li, T., Maserati, M., Lu, S. J., Zdravkovic, T., Ilic, D., Genbacev, O., Fisher, S., Krtolica, A. Lanza, R. 2008. Human embryonic stem cell lines generated without embryo destruction. Cell Stem Cell 2, 113 117.
21. Cole, M. F., Johnstone, S. E., Newman, J. J., Kagey, M. H. Young, R. A. 2008. Tcf3 is an integral component of the core regulatory circuitry of embryonic stem cells. Genes Dev. 22, 746 755.
22. Cowan, C. A., Atienza, J., Melton, D. A. Eggan, K. 2005. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309, 1369 1373.
23. Dannenberg, J. H., van Rossum, A., Schuijff, L. te Riele, H. 2000. Ablation of the retinoblastoma gene family deregulates G(1) control causing immortalization and increased cell turnover under growth-restricting conditions. Genes Dev. 14, 3051 3064.
24. Elling, U., Klasen, C., Eisenberger, T., Anlag, K. Treier, M. 2006. Murine inner cell mass-derived lineages depend on Sall4 function. Proc. Natl. Acad. Sci. U S A 103, 16319 16324.
25. Ema, M., Mori, D., Niwa, H., Hasegawa, Y., Yamanaka, Y., Hitoshi, S., Mimura, J., Kawabe, Y., Hosoya, T., Morita, M., Shimosato, D., Uchida, K., Suzuki, N., Yanagisawa, J., Sogawa, K., Rossant, J., Yamamoto, M., Takahashi, S. Fujii-Kuriyama, Y. 2008. Krüppel-like factor 5 is essential for blastocyst development and the normal self-renewal of mouse ESCs. Cell Stem Cell 3, 555 567.
26. Eminli, S., Utikal, J., Arnold, K., Jaenisch, R. Hochedlinger, K. 2008. Reprogramming of neural progenitor cells into induced pluripotent stem cells in the absence of exogenous Sox2 expression. Stem Cells 26, 2467 2474.
27. Epsztejn-Litman, S., Feldman, N., Abu-Remaileh, M., Shufaro, Y., Gerson, A., Ueda, J., Deplus, R., Fuks, F., Shinkai, Y., Cedar, H. Bergman, Y. 2008. De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes. Nat. Struct. Mol. Biol. 15, 1176 1183.
28. Evans, M. J. Kaufman, M. H. 1981. Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154 156.
29. Evans, P. M., Zhang, W., Chen, X., Yang, J., Bhakat, K. K. Liu, C. 2007. Kruppel-like factor 4 is acetylated by p300 and regulates gene transcription via modulation of histone acetylation. J. Biol. Chem. 282, 33994 34002.
30. Feldman, N., Gerson, A., Fang, J., Li, E., Zhang, Y., Shinkai, Y., Cedar, H. Bergman, Y. 2006. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat. Cell. Biol. 2006 (8 188 194.
31. Feng, B., Jiang, J., Kraus, P., Ng, J. H., Heng, J. C., Chan, Y. S., Yaw, L. P., Zhang, W., Loh, Y. H., Han, J., Vega, V. B., Cacheux-Rataboul, V., Lim, B., Lufkin, T. Ng, H. H. 2009. Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat. Cell Biol. 11, 197 203.
32. Ferri, A. L., Cavallaro, M., Braida, D., Di Cristofano, A., Canta, A., Vezzani, A., Ottolenghi, S., Pandolfi, P. P., Sala, M., DeBiasi, S. Nicolis, S. K. 2004. Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. Development 131, 3805 3819.
33. Gangaraju, V. K. Lin, H. 2009. MicroRNAs: key regulators of stem cells. Nat. Rev. Mol. Cell Biol. 10, 116 125.
34. Guo, G., Yang, J., Nichols, J., Hall, J. S., Eyres, I., Mansfield, W. Smith, A. 2009. Klf4 reverts developmentally programmed restriction of ground state pluripotency. Development 136, 1063 1069.
35. Gurdon, J. B., Elsdale, T. R. Fischber, M. 1958. Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei. Nature 182, 64 65.
36. Hanna, J., Saha, K., Pando, B., van Zon, J., Lengner, CJ., Creyghton, MP., van Oudenaarden, A. Jaenisch, R. 2009. Direct cell reprogramming is a stochastic process amenable to acceleration. Nature. 462, 595 601.
37. Heo, I., Joo, C., Cho, J., Ha, M., Han, J. Kim, V. N. 2008. Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. Mol. Cell 32, 276 284.
38. Heo, I., Joo, C., Kim, Y. K., Ha, M., Yoon, M. J., Cho, J., Yeom, K. H., Han, J. Kim, V. N. 2009. TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell 138, 696 708.
39. Hester, M. E., Song, S., Miranda, C. J., Eagle, A., Schwartz, P. H. Kaspar, B. K. 2009. Two factor reprogramming of human neural stem cells into pluripotency. PLoS ONE 4, e7044.
40. Hochedlinger, K. Jaenisch, R. 2006. Nuclear reprogramming and pluripotency. Nature 441, 1061 1067.
41. Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K. Yamanaka, S. 2009. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460, 1132 1135.
42. Houbaviy, H. B., Murray, M. F. Sharp, P. A. 2003. Embryonic stem cell-specific MicroRNAs. Dev. Cell 5, 351 358.
43. Huangfu, D., Maehr, R., Guo, W., Eijkelenboom, A., Snitow, M., Chen, A. E. Melton, D. A. 2008a. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat. Biotechnol. 26, 795 797.
44. Huangfu, D., Osafune, K., Maehr, R., Guo, W., Eijkelenboom, A., Chen, S., Muhlestein, W. Melton, D. A. 2008b. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat. Biotechnol. 26, 1269 1275.
45. Ichida, J. K., Blanchard, J., Lam, K., Son, E. Y., Chung, J. E., Egli, D., Loh, K. M., Carter, A. C., Di Giorgio, F. P., Koszka, K., Huangfu, D., Akutsu, H., Liu, D. R., Rubin, L. Eggan, K. 2009. A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell. 5, 491 503.
46. Ikegami, K., Iwatani, M., Suzuki, M., Tachibana, M., Shinkai, Y., Tanaka, S., Greally, J. M., Yagi, S., Hattori, N. Shiota, K. 2007. Genome-wide and locus-specific DNA hypomethylation in G9a deficient mouse embryonic stem cells. Genes. Cells 12, 1 11.
47. Ivey, K. N., Muth, A., Arnold, J., King, F. W., Yeh, R. F., Fish, J. E., Hsiao, E. C., Schwartz, R. J., Conklin, B. R., Bernstein, H. S. Srivastava, D. 2008. MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell 2, 219 229.
48. Jackson, M., Krassowska, A., Gilbert, N., Chevassut, T., Forrester, L., Ansell, J. Ramsahoye, B. 2004. Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells. Mol. Cell. Biol. 24, 8862 8871.
49. Jiang, J., Chan, Y. S., Loh, Y. H., Cai, J., Tong, G. Q., Lim, C. A., Robson, P., Zhong, S. Ng, H. H. 2008. A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat. Cell Biol. 10, 353 360.
50. Judson, R. L., Babiarz, J. E., Venere, M. Blelloch, R. 2009. Embryonic stem cell-specific microRNAs promote induced pluripotency. Nat. Biotechnol. 27, 459 461.
51. Kaji, K., Caballero, I. M., MacLeod, R., Nichols, J., Wilson, V. A. Hendrich, B. 2006. The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. Nat. Cell Biol. 8, 285 292.
52. Kanatsu-Shinohara, M., Inoue, K., Lee, J., Yoshimoto, M., Ogonuki, N., Miki, H., Baba, S., Kato, T., Kazuki, Y., Toyokuni, S., Toyoshima, M., Niwa, O., Oshimura, M., Heike, T., Nakahata, T., Ishino, F., Ogura, A. Shinohara, T. 2004. Generation of pluripotent stem cells from neonatal mouse testis. Cell 119, 1001 1012.
53. Kanellopoulou, C., Muljo, S. A., Kung, A. L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D. M. Rajewsky, K. 2005. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev. 19, 489 501.
54. Kang, L., Wang, J., Zhang, Y., Kou, Z. Gao, S. 2009. iPS cells can support full-term development of tetraploid blastocyst-complemented embryos. Cell Stem Cell 5, 135 138.
55. Kawamura, T., Suzuki, J., Wang, Y. V., Menendez, S., Morera, L. B., Raya, A., Wahl, G. M. Izpisúa Belmonte, J. C. 2009. Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460, 1140 1144.
56. Kawasaki, H., Mizuseki, K., Nishikawa, S., Kaneko, S., Kuwana, Y., Nakanishi, S., Nishikawa, S. I. Sasai, Y. 2000. Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28, 31 40.
57. Kehler, J., Tolkunova, E., Koschorz, B., Pesce, M., Gentile, L., Boiani, M., Lomelí, H., Nagy, A., McLaughlin, K. J., Schöler, H. R. Tomilin, A. 2004. Oct4 is required for primordial germ cell survival. EMBO Rep. 5, 1078 1083.
58. Kim, H. H., Kuwano, Y., Srikantan, S., Lee, E. K., Martindale, J. L. Gorospe, M. 2009a. HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev. 23, 1743 1748.
59. Kim, J. B., Zaehres, H., Wu, G., Gentile, L., Ko, K., Sebastiano, V., Araúzo-Bravo, M. J., Ruau, D., Han, D. W., Zenke, M. Schöler, H. R. 2008. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 454, 646 650.
60. Kim, J. B., Sebastiano, V., Wu, G., Araúzo-Bravo, M. J., Sasse, P., Gentile, L., Ko, K., Ruau, D., Ehrich, M., van den Boom, D., Meyer, J., Hübner, K., Bernemann, C., Ortmeier, C., Zenke, M., Fleischmann, B. K., Zaehres, H. Schöler, H. R. 2009b. Oct4-induced pluripotency in adult neural stem cells. Cell 136, 411 419.
61. Kim, J. B., Greber, B., Araúzo-Bravo, M. J., Meyer, J., Park, K. I., Zaehres, H. Schöler, H. R. 2009c. Direct reprogramming of human neural stem cells by OCT4. Nature 461, 649 653.
62. Kimura, H., Tada, M., Nakatsuji, N. Tada, T. 2004. Histone code modifications on pluripotential nuclei of reprogrammed somatic cells. Mol. Cell. Biol. 24, 5710 5720.
63. Kishigami, S., Mizutani, E., Ohta, H., Hikichi, T., Van Thuan, N., Wakayama, S., Bui, H. T. Wakayama, T. 2006. Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer. Biochem. Biophys. Res. Commun. 340, 183 189.
64. Klimanskaya, I., Chung, Y., Becker, S., Lu, S. J. Lanza, R. 2006. Human embryonic stem cell lines derived from single blastomeres. Nature 444, 481 485.
65. Labosky, P. A., Barlow, D. P. Hogan, B. L. 1994. Mouse embryonic germ (EG) cell lines: transmission through the germline and differences in the methylation imprint of insulin-like growth factor 2 receptor (Igf2r) gene compared with embryonic stem (ES) cell lines. Development 120, 3197 3204.
66. LeCouter, J. E., Whyte, P. F. Rudnicki, M. A. 1996. Cloning and expression of the Rb-related mouse p130 mRNA. Oncogene 12, 1433 1440.
67. Lee, T. I., Jenner, R. G., Boyer, L. A., Guenther, M. G., Chevalier, B., Levine, S. S., Kumar, R. M., Johnstone, S. E., Murray, H. L., Zucker, J. P., Yuan, B., Bell, G. W., Herbolsheimer, E., Hannett, N. M., Cole, M. F., Sun, K., Odom, D. T., Volkert, T. L., Bartel, D. P., Gifford, D. K., Melton, D. A., Jaenisch, R. Young, R. A. 2006. Control of developmental regulators by polycomb in human embryonic stem cells. Cell 125, 301 313.
68. Li, E. 2002. Chromatin modification and epigenetic reprogramming in mammalian development. Nat. Rev. Genet. 3, 662 673.
69. Li, W., Zhou, H., Abujarour, R., Zhu, S., Joo, J. Y., Lin, T., Hao, E., Schöler, H. R., Hayek, A. Ding, S. 2009a. Generation of human induced pluripotent stem cells in the absence of exogenous Sox2. Stem Cells 27, 2992 3000.
70. Li, Y., McClintick, J., Zhong, L., Edenberg, H. J., Yoder, M. C. Chan, R. J. 2005. Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4. Blood 105, 635 637.
71. Li, H., Collado, M., Villasante, A., Strati, K., Ortega, S., Cañamero, M., Blasco, M. A. Serrano, M. 2009b. The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460, 1136 1139.
72. Liao, J., Wu, Z., Wang, Y., Cheng, L., Cui, C., Gao, Y., Chen, T., Rao, L., Chen, S., Jia, N., Dai, H., Xin, S., Kang, J., Pei, G. Xiao, L. 2008. Enhanced efficiency of generating induced pluripotent stem (iPS) cells from human somatic cells by a combination of six transcription factors. Cell Res. 18, 600 603.
73. Lin, C. H., Lin, C., Tanaka, H., Fero, M. L. Eisenman, R. N. 2009a. Gene regulation and epigenetic remodeling in murine embryonic stem cells by c-Myc. PLoS ONE 4, e7839.
74. Lin, T., Chao, C., Saito, S., Mazur, S. J., Murphy, M. E., Appella, E. Xu, Y. 2005. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat. Cell Biol. 7, 165 171.
75. Lin, T., Ambasudhan, R., Yuan, X., Li, W., Hilcove, S., Abujarour, R., Lin, X., Hahm, H. S., Hao, E., Hayek, A. Ding, S. 2009b. A chemical platform for improved induction of human iPSCs. Nat. Methods 6, 805 808.
76. Lukas, J., Parry, D., Aagaard, L., Mann, D. J., Bartkova, J., Strauss, M., Peters, G. Bartek, J. 1995. Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16. Nature 375, 503 506.
77. Lyssiotis, C. A., Foreman, R. K., Staerk, J., Garcia, M., Mathur, D., Markoulaki, S., Hanna, J., Lairson, L. L., Charette, B. D., Bouchez, L. C., Bollong, M., Kunick, C., Brinker, A., Cho, C. Y., Schultz, P. G. Jaenisch, R. 2009. Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4. Proc. Natl. Acad. Sci. U S A 106, 8912 8917.
78. Ma, D. K., Chiang, C. H., Ponnusamy, K., Ming, G. L. Song, H. 2008. G9a and Jhdm2a regulate embryonic stem cell fusion-induced reprogramming of adult neural stem cells. Stem Cells 26, 2131 2141.
79. Maherali, N., Sridharan, R., Xie, W., Utikal, J., Eminli, S., Arnold, K., Stadtfeld, M., Yachechko, R., Tchieu, J., Jaenisch, R., Plath, K. Hochedlinger, K. 2007. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1, 55 70.
80. Maherali, N. Hochedlinger, K. 2009. Tgfbeta signal inhibition cooperates in the induction of iPSCs and replaces Sox2 and cMyc. Curr. Biol. 19, 1718 1723.
81. Mali, P., Ye, Z., Hommond, H. H., Yu, X., Lin, J., Chen, G., Zou, J. Cheng, L. 2008. Improved efficiency and pace of generating induced pluripotent stem cells from human adult and fetal fibroblasts. Stem Cells 26, 1998 2005.
82. Marión, R. M., Strati, K., Li, H., Murga, M., Blanco, R., Ortega, S., Fernandez-Capetillo, O., Serrano, M. Blasco, M. A. 2009. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460, 1149 1153.
83. 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 7638.
84. Masui, S., Nakatake, Y., Toyooka, Y., Shimosato, D., Yagi, R., Takahashi, K., Okochi, H., Okuda, A., Matoba, R., Sharov, A. A., Ko, M. S. Niwa, H. 2007. Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat. Cell Biol. 9, 625 635.
85. Marson, A., Foreman, R., Chevalier, B., Bilodeau, S., Kahn, M., Young, R. A. Jaenisch, R. 2008. Wnt signaling promotes reprogramming of somatic cells to pluripotency. Cell Stem Cell 3, 132 135.
86. Maruyama, M., Ichisaka, T., Nakagawa, M. Yamanaka, S. 2005. Differential roles for Sox15 and Sox2 in transcriptional control in mouse embryonic stem cells. J. Biol. Chem. 280, 24371 24379.
87. Matsuda, T., Nakamura, T., Nakao, K., Arai, T., Katsuki, M., Heike, T. Yokota, T. 1999. STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells. EMBO J. 18, 4261 4269.
88. Matsui, Y., Zsebo, K. Hogan, B. L. 1992. Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell 70, 841 847.
89. McLaren, A. 2007. A scientist's view of the ethics of human embryonic stem cell research. Cell Stem Cell 1, 23 26.
90. Medema, R. H., Herrera, R. E., Lam, F. Weinberg, R. A. 1995. Growth suppression by p16ink4 requires functional retinoblastoma protein. Proc. Natl. Acad. Sci. U S A 92, 6289 6293.
91. Mikkelsen, T. S., Hanna, J., Zhang, X., Ku, M., Wernig, M., Schorderet, P., Bernstein, B. E., Jaenisch, R., Lander, E. S. Meissner, A. 2008. Dissecting direct reprogramming through integrative genomic analysis. Nature 454, 49 55.
92. Mitsui, K., Tokuzawa, Y., Itoh, H., Segawa, K., Murakami, M., Takahashi, K., Maruyama, M., Maeda, M. Yamanaka, S. 2003. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113, 631 642.
93. Montalto, M. C., Phillips, J. S. Ray, F. A. 1999. Telomerase activation in human fibroblasts during escape from crisis. J. Cell. Physiol. 180, 46 52.
94. Morgan, H. D., Dean, W., Coker, H. A., Reik, W. Petersen-Mahrt, S. K. 2004. Activation-induced cytidine deaminase deaminates 5-Methylcytocine in DNA and is expressed in pluripotent tissues. J. Biol. Chem. 279, 52353 52360.
95. Murchison, E. P., Partridge, J. F., Tam, O. H., Cheloufi, S. Hannon, G. J. 2005. Characterization of Dicer-deficient murine embryonic stem cells. Proc. Natl. Acad. Sci. U S A 102, 12135 12140.
96. Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., Okita, K., Mochiduki, Y., Takizawa, N. Yamanaka, S. 2008. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat. Biotechnol. 26, 101 106.
97. Nakajima, F., Tokunaga, K. Nakatsuji, N. 2007. Human leukocyte antigen matching estimations in a hypothetical bank of human embryonic stem cell lines in the Japanese population for use in cell transplantation therapy. Stem Cells 25, 983 985.
98. Nakano, T., Kodama, H. Honjo, T. 1996. In vitro development of primitive and definitive erythrocytes from different precursors. Science 272, 722 724.
99. Nakatake, Y., Fukui, N., Iwamatsu, Y., Masui, S., Takahashi, K., Yagi, R., Yagi, K., Miyazaki, J., Matoba, R., Ko, M. S. Niwa, H. 2006. Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol. Cell. Biol. 26, 7772 7782.
100. Nichols, J., Zevnik, B., Anastassiadis, K., Niwa, H., Klewe-Nebenius, D., Chambers, I., Schöler, H. Smith, A. 1998. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95, 379 391.
101. Niwa, H., Burdon, T., Chambers, I. Smith, A. 1998. Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev. 12, 2048 2060.
102. Niwa, H., Miyazaki, J. Smith, A. G. 2000. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat. Genet. 24, 372 376.
103. Niwa, H., Ogawa, K., Shimosato, D. Adachi, K. 2009. A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. Nature 460, 118 122.
104. Okita, K., Ichisaka, T. Yamanaka, S. 2007. Generation of germline-competent induced pluripotent stem cells. Nature 448, 313 317.
105. Papapetrou, E. P., Tomishima, M. J., Chambers, S. M., Mica, Y., Reed, E., Menon, J., Tabar, V., Mo, Q., Studer, L. Sadelain, M. 2009. Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation. Proc. Natl. Acad. Sci. U S A 106, 12759 12764.
106. Park, I. H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H., Ince, T. A., Lerou, P. H., Lensch, M. W. Daley, G. Q. 2008. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451, 141 146.
107. Pereira, L., Yi, F. Merrill, B. J. 2006. Repression of Nanog gene transcription by Tcf3 limits embryonic stem cell self-renewal. Mol. Cell. Biol. 26, 7479 7491.
108. Qin, H., Yu, T., Qing, T., Liu, Y., Zhao, Y., Cai, J., Li, J., Song, Z., Qu, X., Zhou, P., Wu, J., Ding, M. Deng, H. 2007. Regulation of apoptosis and differentiation by p53 in human embryonic stem cells. J. Biol. Chem. 282, 5842 5852.
109. Rideout III., W. M., Wakayama, T., Wutz, A., Eggan, K., Jackson-Grusby, L., Dausman, J., Yanagimachi, R. Jaenisch, R. 2000. Generation of mice from wild-type and targeted ES cells by nuclear cloning. Nat. Genet. 24, 109 110.
110. Rideout III., W. M., Hochedlinger, K., Kyba, M., Daley, G. Q. Jaenisch, R. 2002. Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy. Cell 109, 17 27.
111. Robanus-Maandag, E., Dekker, M., van der Valk, M., Carrozza, M. L., Jeanny, J. C., Dannenberg, J. H., Berns, A. te Riele, H. 1998. p107 is a suppressor of retinoblastoma development in pRb-deficient mice. Genes Dev. 12, 1599 1609.
112. Rowland, B. D., Bernards, R. Peeper, D. S. 2005. The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene. Nat. Cell Biol. 7, 1074 1082.
113. Rybouchkin, A., Kato, Y. Tsunoda, Y. 2006. Role of histone acetylation in reprogramming of somatic nuclei following nuclear transfer. Biol. Reprod. 74, 1083 1089.
114. Sabapathy, K., Klemm, M., Jaenisch, R. Wagner, E. F. 1997. Regulation of ES cell differentiation by functional and conformational modulation of p53. EMBO J. 16, 6217 6229.
115. Sage, J., Mulligan, G. J., Attardi, L. D., Miller, A., Chen, S., Williams, B., Theodorou, E. Jacks, T. 2000. Targeted disruption of the three Rb-related genes leads to loss of G(1) control and immortalization. Genes Dev. 14, 3037 3050.
116. Sakaki-Yumoto, M., Kobayashi, C., Sato, A., Fujimura, S., Matsumoto, Y., Takasato, M., Kodama, T., Aburatani, H., Asashima, M., Yoshida, N. Nishinakamura, R. 2006. The murine homolog of SALL4, a causative gene in Okihiro syndrome, is essential for embryonic stem cell proliferation, and cooperates with Sall1 in anorectal, heart, brain and kidney development. Development 133, 3005 3013.
117. Sato, N., Meijer, L., Skaltsounis, L., Greengard, P. Brivanlou, A. H. 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.
118. Savatier, P., Lapillonne, H., van Grunsven, L. A., Rudkin, B. B. Samarut, J. 1996. Withdrawal of differentiation inhibitory activity/leukemia inhibitory factor up-regulates D-type cyclins and cyclin-dependent kinase inhibitors in mouse embryonic stem cells. Oncogene 12, 309 322.
119. Shi, Y., Do, J. T., Desponts, C., Hahm, H. S., Schöler, H. R. Ding, S. 2008a. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell 2, 525 528.
120. Shi, Y., Desponts, C., Do, J. T., Hahm, H. S., Schöler, H. R. Ding, S. 2008b. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3, 568 574.
121. Singh, A. M. Dalton, S. 2009. The cell cycle and Myc intersect with mechanisms that regulate pluripotency and reprogramming. Cell Stem Cell 5, 141 149.
122. Smith, A. G., Heath, J. K., Donaldson, D. D., Wong, G. G., Moreau, J., Stahl, M. Rogers, D. 1988. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336, 688 690.
123. Silva, J., Chambers, I., Pollard, S. Smith, A. 2006. Nanog promotes transfer of pluripotency after cell fusion. Nature 441, 997 1001.
124. Silva, J., Barrandon, O., Nichols, J., Kawaguchi, J., Theunissen, T. W. Smith, A. 2008. Promotion of reprogramming to ground state pluripotency by signal inhibition. PLoS Biol. 6, e253.
125. Smith, A. G. 2001. Embryo-derived stem cells: of mice and men. Annu. Rev. Cell. Dev. Biol. 17, 435 462.
126. Sridharan, R., Tchieu, J., Mason, M. J., Yachechko, R., Kuoy, E., Horvath, S., Zhou, Q. Plath, K. 2009. Role of the murine reprogramming factors in the induction of pluripotency. Cell 136, 364 377.
127. Stewart, S. A. Weinberg, R. A. 2006. Telomeres: cancer to human aging. Annu. Rev. Cell. Dev. Biol. 22, 531 557.
128. Su, H., Trombly, M. I., Chen, J. Wang, X. 2009. Essential and overlapping functions for mammalian Argonautes in microRNA silencing. Genes Dev. 23, 304 317.
129. Suh, M. R., Lee, Y., Kim, J. Y., Kim, S. K., Moon, S. H., Lee, J. Y., Cha, K. Y., Chung, H. M., Yoon, H. S., Moon, S. Y., Kim, V. N. Kim, K. S. 2004. Human embryonic stem cells express a unique set of microRNAs. Dev. Biol. 270, 488 498.
130. Sumi, T., Fujimoto, Y., Nakatsuji, N. Suemori, H. 2004. STAT3 is dispensable for maintenance of self-renewal in nonhuman primate embryonic stem cells. Stem Cells 22, 861 872.
131. Sumi, T., Tsuneyoshi, N., Nakatsuji, N. Suemori, H. 2007. Apoptosis and differentiation of human embryonic stem cells induced by sustained activation of c-Myc. Oncogene 26, 5564 5576.
132. Tachibana, M., Sugimoto, K., Nozaki, M., Ueda, J., Ohta, T., Ohki, M., Fukuda, M., Takeda, N., Niida, H., Kato, H. Shinkai, Y. 2002. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev. 16, 1779 1791.
133. Tada, M., Takahama, Y., Abe, K., Nakatsuji, N. Tada, T. 2001. Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr. Biol. 11, 1553 1558.
134. Takagi, N., Yoshida, M. A., Sugawara, O. Sasaki, M. 1983. Reversal of X-inactivation in female mouse somatic cells hybridized with murine teratocarcinoma stem cells in vitro. Cell 34, 1053 1062.
135. Takahashi, K. Yamanaka, S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663 676.
136. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K. Yamanaka, S. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861 872.
137. Tam, W. L., Lim, C. Y., Han, J., Zhang, J., Ang, Y. S., Ng, H. H., Yang, H. Lim, B. 2008. T-cell factor 3 regulates embryonic stem cell pluripotency and self-renewal by the transcriptional control of multiple lineage pathways. Stem Cells 26, 2019 2031.
138. Taranova, O. V., Magness, S. T., Fagan, B. M., Wu, Y., Surzenko, N., Hutton, S. R. Pevny, L. H. 2006. SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Genes Dev. 20, 1187 1202.
139. Tay, Y., Zhang, J., Thomson, A. M., Lim, B. Rigoutsos, I. 2008. MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455, 1124 1128.
140. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S. Jones, J. M. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145 1147.
141. Tsubooka, N., Ichisaka, T., Okita, K., Takahashi, K., Nakagawa, M. Yamanaka, S. 2009. Roles of Sall4 in the generation of pluripotent stem cells from blastocysts and fibroblasts. Genes Cells 14, 683 694.
142. Tsumura, A., Hayakawa, T., Kumaki, Y., Takebayashi, S., Sakaue, M., Matsuoka, C., Shimotohno, K., Ishikawa, F., Li, E., Ueda, H. R., Nakayama, J. Okano, M. 2006. Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Genes Cells 11, 805 814.
143. Ura, H., Usuda, M., Kinoshita, K., Sun, C., Mori, K., Akagi, T., Matsuda, T., Koide, H. Yokota, T. 2008. STAT3 and Oct-3/4 control histone modification through induction of Eed in embryonic stem cells. J. Biol. Chem. 283, 9713 9723.
144. Utikal, J., Maherali, N., Kulalert, W. Hochedlinger, K. 2009a. Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells. J. Cell Sci. 122, 3502 3510.
145. Utikal, J., Polo, J. M., Stadtfeld, M., Maherali, N., Kulalert, W., Walsh, R. M., Khalil, A., Rheinwald, J. G. Hochedlinger, K. 2009b. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460, 1145 1148.
146. Van Thuan, N., Bui, H. T., Kim, J. H., Hikichi, T., Wakayama, S., Kishigami, S., Mizutani, E. Wakayama, T. 2009. The histone deacetylase inhibitor scriptaid enhances nascent mRNA production and rescues full-term development in cloned inbred mice. Reproduction 138, 309 317.
147. Viswanathan, S. R., Daley, G. Q. Gregory, R. I. 2008. Selective blockade of microRNA processing by Lin28. Science 320, 97 100.
148. Viswanathan, S. R., Powers, J. T., Einhorn, W., Hoshida, Y., Ng, T. L., Toffanin, S., O'Sullivan, M., Lu, J., Phillips, L. A., Lockhart, V. L., Shah, S. P., Tanwar, P. S., Mermel, C. H., Beroukhim, R., Azam, M., Teixeira, J., Meyerson, M., Hughes, T. P., Llovet, J. M., Radich, J., Mullighan, C. G., Golub, T. R., Sorensen, P. H. Daley, G. Q. 2009. Lin28 promotes transformation and is associated with advanced human malignancies. Nat. Genet. 41, 843 848.
149. Wang, Y., Medvid, R., Melton, C., Jaenisch, R. Blelloch, R. 2007. DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat. Genet. 39, 380 385.
150. Wang, Y., Baskerville, S., Shenoy, A., Babiarz, J. E., Baehner, L. Blelloch, R. 2008. Embryonic stem cell-specific microRNAs regulate the G1-S transition and promote rapid proliferation. Nat. Genet. 40, 1478 1483.
151. Wei, Z., Yang, Y., Zhang, P., Andrianakos, R., Hasegawa, K., Lyu, J., Chen, X., Bai, G., Liu, C., Pera, M. Lu, W. 2009. Klf4 interacts directly with Oct4 and Sox2 to promote reprogramming. Stem Cells 27, 2969 2978.
152. Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., Bernstein, B. E. Jaenisch, R. 2007. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448, 318 324.
153. Wernig, M., Meissner, A., Cassady, J. P. Jaenisch, R. 2008a. c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell 2, 10 12.
154. Wernig, M., Lengner, C. J., Hanna, J., Lodato, M. A., Steine, E., Foreman, R., Staerk, J., Markoulaki, S. Jaenisch, R. 2008b. A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nat. Biotechnol. 26, 916 924.
155. Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J. Campbell, K. H. 1997. Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810 813.
156. Wong, C. C., Gaspar-Maia, A., Ramalho-Santos, M. Reijo Pera, R. A. 2008. High-efficiency stem cell fusion-mediated assay reveals Sall4 as an enhancer of reprogramming. PLoS ONE 3, e1955.
157. Woltjen, K., Michael, I. P., Mohseni, P., Desai, R., Mileikovsky, M., Hämäläinen, R., Cowling, R., Wang, W., Liu, P., Gertsenstein, M., Kaji, K., Sung, H. K. Nagy, A. 2009. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458, 766 770.
158. Wu, Q., Chen, X., Zhang, J., Loh, Y. H., Low, T. Y., Zhang, W., Zhang, W., Sze, S. K., Lim, B. Ng, H. H. 2006. Sall4 interacts with Nanog and co-occupies Nanog genomic sites in embryonic stem cells. J. Biol. Chem. 281, 24090 24094.
159. Xu, N., Papagiannakopoulos, T., Pan, G., Thomson, J. A. Kosik, K. S. 2009. MicroRNA-145 regulates OCT4, SOX2, and KLF4 and represses pluripotency in human embryonic stem cells. Cell 137, 647 658.
160. Yamanaka, S. 2009. Elite and stochastic models for induced pluripotent stem cell generation. Nature 460, 49 52.
161. Yamashita, J., Itoh, H., Hirashima, M., Ogawa, M., Nishikawa, S., Yurugi, T., Naito, M., Nakao, K. Nishikawa, S. 2000. Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature 408, 92 96.
162. Yasuda, S. Y., Tsuneyoshi, N., Sumi, T., Hasegawa, K., Tada, T., Nakatsuji, N. Suemori, H. 2006. NANOG maintains self-renewal of primate ES cells in the absence of a feeder layer. Genes. Cells 11, 1115 1123.
163. Yi, F., Pereira, L. Merrill, B. J. 2008. Tcf3 functions as a steady-state limiter of transcriptional programs of mouse embryonic stem cell self-renewal. Stem Cells 26, 1951 1960.
164. Ying, Q. L., Wray, J., Nichols, J., Batlle-Morera, L., Doble, B., Woodgett, J., Cohen, P. Smith, A. 2008. The ground state of embryonic stem cell self-renewal. Nature 453, 519 523.
165. Yoshida, Y., Takahashi, K., Okita, K., Ichisaka, T. Yamanaka, S. 2009. Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell 5, 237 241.
166. Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., Slukvin, I. I. Thomson, J. A. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917 1920.
167. Yu, J., Hu, K., Smuga-Otto, K., Tian, S., Stewart, R., Slukvin, I. I. Thomson, J. A. 2009. Human induced pluripotent stem cells free of vector and transgene sequences. Science 324, 797 801.
168. Zhang, J., Tam, W. L., Tong, G. Q., Wu, Q., Chan, H. Y., Soh, B. S., Lou, Y., Yang, J., Ma, Y., Chai, L., Ng, H. H., Lufkin, T., Robson, P. Lim, B. 2006. Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat. Cell Biol. 8, 1114 1123.
169. Zhang, X., Zhang, J., Wang, T., Esteban, M. A. Pei, D. 2008. Esrrb activates Oct4 transcription and sustains self-renewal and pluripotency in embryonic stem cells. J. Biol. Chem. 283, 35825 35833.
170. Zhao, X. Y., Li, W., Lv, Z., Liu, L., Tong, M., Hai, T., Hao, J., Guo, C. L., Ma, Q. W., Wang, L., Zeng, F. Zhou, Q. 2009. iPS cells produce viable mice through tetraploid complementation. Nature 461, 86 90.
171. Zhao, Y., Samal, E. Srivastava, D. 2005. Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436, 214 220.
172. Zhou, Q., Chipperfield, H., Melton, D. A. Wong, W. H. 2007. A gene regulatory network in mouse embryonic stem cells. Proc. Natl. Acad. Sci. U S A 104, 16438 16443.