The genomic stability of induced pluripotent stem cells

Zhao Chen, Tongbiao Zhao, Yang Xu()

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PDF(183 KB)
Protein Cell ›› 2012, Vol. 3 ›› Issue (4) : 271-277. DOI: 10.1007/s13238-012-2922-8
MINI-REVIEW
MINI-REVIEW

The genomic stability of induced pluripotent stem cells

  • Zhao Chen, Tongbiao Zhao, Yang Xu()
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Abstract

With their capability to undergo unlimited self-renewal and to differentiate into all cell types in the body, induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells of human patients with defined factors, hold promise for regenerative medicine because they can provide a renewable source of autologous cells for cell therapy without the concern for immune rejection. In addition, iPSCs provide a unique opportunity to model human diseases with complex genetic traits, and a panel of human diseases have been successfully modeled in vitro by patient-specific iPSCs. Despite these progresses, recent studies have raised the concern for genetic and epigenetic abnormalities of iPSCs that could contribute to the immunogenicity of some cells differentiated from iPSCs. The oncogenic potential of iPSCs is further underscored by the findings that the critical tumor suppressor p53, known as the guardian of the genome, suppresses induced pluripotency. Therefore, the clinic application of iPSCs will require the optimization of the reprogramming technology to minimize the genetic and epigenetic abnormalities associated with induced pluripotency.

Keywords

induced pluripotent stem cells / reprogramming / genetic and epigenetic abnormalities

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Zhao Chen, Tongbiao Zhao, Yang Xu. The genomic stability of induced pluripotent stem cells. Prot Cell, 2012, 3(4): 271‒277 https://doi.org/10.1007/s13238-012-2922-8

References

[1] Aasen, T., Raya, A., Barrero, M.J., Garreta, E., Consiglio, A., Gonzalez, F., Vassena, R., Bili?, J., Pekarik, V., Tiscornia, G., . (2008). Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26, 1276-1284 .10.1038/nbt.1503
[2] Agarwal, S., Loh, Y.H., McLoughlin, E.M., Huang, J., Park, I.H., Miller, J.D., Huo, H., Okuka, M., Dos Reis, R.M., Loewer, S., . (2010). Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 464, 292-296 .10.1038/nature08792
[3] Aoi, T., Yae, K., Nakagawa, M., Ichisaka, T., Okita, K., Takahashi, K., Chiba, T., and Yamanaka, S. (2008). Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321, 699-702 .10.1126/science.1154884
[4] Avilion, A.A., Nicolis, S.K., Pevny, L.H., Perez, L., Vivian, N., and Lovell-Badge, R. (2003). Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev 17, 126-140 .10.1101/gad.224503
[5] Banito, A., Rashid, S.T., Acosta, J.C., Li, S., Pereira, C.F., Geti, I., Pinho, S., Silva, J.C., Azuara, V., Walsh, M., . (2009). Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev 23, 2134-2139 .10.1101/gad.1811609
[6] Bass, A.J., Watanabe, H., Mermel, C.H., Yu, S., Perner, S., Verhaak, R.G., Kim, S.Y., Wardwell, L., Tamayo, P., Gat-Viks, I., . (2009). SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet 41, 1238-1242 .10.1038/ng.465
[7] Bedell, M.A., Jenkins, N.A., and Copeland, N.G. (1997a). Mouse models of human disease. Part I: techniques and resources for genetic analysis in mice. Genes Dev 11, 1-10 .10.1101/gad.11.1.1
[8] Bedell, M.A., Largaespada, D.A., Jenkins, N.A., and Copeland, N.G. (1997b). Mouse models of human disease. Part II: recent progress and future directions. Genes Dev 11, 11-43 .10.1101/gad.11.1.11
[9] Boland, M.J., Hazen, J.L., Nazor, K.L., Rodriguez, A.R., Gifford, W., Martin, G., Kupriyanov, S., and Baldwin, K.K. (2009). Adult mice generated from induced pluripotent stem cells. Nature 461, 91-94 .10.1038/nature08310
[10] 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., . (2005). Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122, 947-956 .10.1016/j.cell.2005.08.020
[11] Brennand, K.J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., Li, Y., Mu, Y., Chen, G., Yu, D., . (2011). Modelling schizophrenia using human induced pluripotent stem cells. Nature 473, 221-225 .10.1038/nature09915
[12] Carvajal-Vergara, X., Sevilla, A., D’Souza, S.L., Ang, Y.S., Schaniel, C., Lee, D.F., Yang, L., Kaplan, A.D., Adler, E.D., Rozov, R., . (2010). Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 465, 808-812 .10.1038/nature09005
[13] Chambers, I., Colby, D., Robertson, M., Nichols, J., Lee, S., Tweedie, S., and Smith, A. (2003). Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113, 643-655 .10.1016/S0092-8674(03)00392-1
[14] Chiou, S.H., Wang, M.L., Chou, Y.T., Chen, C.J., Hong, C.F., Hsieh, W.J., Chang, H.T., Chen, Y.S., Lin, T.W., Hsu, H.S., . (2010). Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res 70, 10433-10444 .10.1158/0008-5472.CAN-10-2638
[15] Dang, C.V., O’Donnell, K.A., Zeller, K.I., Nguyen, T., Osthus, R.C., and Li, F. (2006). The c-Myc target gene network. Semin Cancer Biol 16, 253-264 .10.1016/j.semcancer.2006.07.014
[16] Dang, D.T., Pevsner, J., and Yang, V.W. (2000). The biology of the mammalian Krüppel-like family of transcription factors. Int J Biochem Cell Biol 32, 1103-1121 .10.1016/S1357-2725(00)00059-5
[17] Dimos, J.T., Rodolfa, K.T., Niakan, K.K., Weisenthal, L.M., Mitsumoto, H., Chung, W., Croft, G.F., Saphier, G., Leibel, R., Goland, R., . (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321, 1218-1221 .10.1126/science.1158799
[18] Ebert, A.D., Yu, J., Rose, F.F. Jr, Mattis, V.B., Lorson, C.L., Thomson, J.A., and Svendsen, C.N. (2009). Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457, 277-280 .10.1038/nature07677
[19] Eminli, S., Foudi, A., Stadtfeld, M., Maherali, N., Ahfeldt, T., Mostoslavsky, G., Hock, H., and Hochedlinger, K. (2009). Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat Genet 41, 968-976 .10.1038/ng.428
[20] Eminli, S., Utikal, J., Arnold, K., Jaenisch, R., and 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 .10.1634/stemcells.2008-0317
[21] Esteban, M.A., Wang, T., Qin, B., Yang, J., Qin, D., Cai, J., Li, W., Weng, Z., Chen, J., Ni, S., . (2010). Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 6, 71-79 .10.1016/j.stem.2009.12.001
[22] Esteban, M.A., Xu, J., Yang, J., Peng, M., Qin, D., Li, W., Jiang, Z., Chen, J., Deng, K., Zhong, M., . (2009). Generation of induced pluripotent stem cell lines from Tibetan miniature pig. J Biol Chem 284, 17634-17640 .10.1074/jbc.M109.008938
[23] Fu, X., and Xu, Y. (2011). Self-renewal and scalability of human embryonic stem cells for human therapy. Regen Med 6, 327-334 .10.2217/rme.11.18
[24] Gidekel, S., Pizov, G., Bergman, Y., and Pikarsky, E. (2003). Oct-3/4 is a dose-dependent oncogenic fate determinant. Cancer Cell 4, 361-370 .10.1016/S1535-6108(03)00270-8
[25] Gore, A., Li, Z., Fung, H.L., Young, J.E., Agarwal, S., Antosiewicz-Bourget, J., Canto, I., Giorgetti, A., Israel, M.A., Kiskinis, E., . (2011). Somatic coding mutations in human induced pluripotent stem cells. Nature 471, 63-67 .10.1038/nature09805
[26] Hanna, J., Markoulaki, S., Schorderet, P., Carey, B.W., Beard, C., Wernig, M., Creyghton, M.P., Steine, E.J., Cassady, J.P., Foreman, R., . (2008). Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 133, 250-264 .10.1016/j.cell.2008.03.028
[27] Hanna, J., Saha, K., Pando, B., van Zon, J., Lengner, C.J., Creyghton, M.P., van Oudenaarden, A., and Jaenisch, R. (2009). Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462, 595-601 .10.1038/nature08592
[28] Hart, A.H., Hartley, L., Parker, K., Ibrahim, M., Looijenga, L.H., Pauchnik, M., Chow, C.W., and Robb, L. (2005). The pluripotency homeobox gene NANOG is expressed in human germ cell tumors. Cancer 104, 2092-2098 .10.1002/cncr.21435
[29] Hochedlinger, K., Yamada, Y., Beard, C., and Jaenisch, R. (2005). Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121, 465-477 .10.1016/j.cell.2005.02.018
[30] Hong, H., Takahashi, K., Ichisaka, T., Aoi, T., Kanagawa, O., Nakagawa, M., Okita, K., and Yamanaka, S. (2009). Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460, 1132-1135 .10.1038/nature08235
[31] Huangfu, D., Maehr, R., Guo, W., Eijkelenboom, A., Snitow, M., Chen, A.E., and Melton, D.A. (2008). Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26, 795-797 .10.1038/nbt1418
[32] Hussein, S.M., Batada, N.N., Vuoristo, S., Ching, R.W., Autio, R., N?rv?, E., Ng, S., Sourour, M., H?m?l?inen, R., Olsson, C., . (2011). Copy number variation and selection during reprogramming to pluripotency. Nature 471, 58-62 .10.1038/nature09871
[33] 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., . (2009). A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell 5, 491-503 .10.1016/j.stem.2009.09.012
[34] Israel, M.A., Yuan, S.H., Bardy, C., Reyna, S.M., Mu, Y., Herrera, C., Hefferan, M.P., Van Gorp, S., Nazor, K.L., Boscolo, F.S., . (2012). Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature 482, 216-220 .
[35] Itzhaki, I., Maizels, L., Huber, I., Zwi-Dantsis, L., Caspi, O., Winterstern, A., Feldman, O., Gepstein, A., Arbel, G., Hammerman, H., . (2011). Modelling the long QT syndrome with induced pluripotent stem cells. Nature 471, 225-229 .10.1038/nature09747
[36] Kang, L., Wang, J., Zhang, Y., Kou, Z., and Gao, S. (2009). iPS cells can support full-term development of tetraploid blastocyst-complemented embryos. Cell Stem Cell 5, 135-138 .10.1016/j.stem.2009.07.001
[37] Kawamura, T., Suzuki, J., Wang, Y.V., Menendez, S., Morera, L.B., Raya, A., Wahl, G.M., and Belmonte, J.C. (2009). Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460, 1140-1144 .10.1038/nature08311
[38] Kim, J.B., Zaehres, H., Wu, G., Gentile, L., Ko, K., Sebastiano, V., Araúzo-Bravo, M.J., Ruau, D., Han, D.W., Zenke, M., . (2008). Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 454, 646-650 .10.1038/nature07061
[39] Kim, K., Doi, A., Wen, B., Ng, K., Zhao, R., Cahan, P., Kim, J., Aryee, M.J., Ji, H., Ehrlich, L.I., . (2010). Epigenetic memory in induced pluripotent stem cells. Nature 467, 285-290 .10.1038/nature09342
[40] Ko, L.J., and Prives, C. (1996). p53: puzzle and paradigm. Genes Dev 10, 1054-1072 .10.1101/gad.10.9.1054
[41] Lake, B.B., Fink, J., Klemetsaune, L., Fu, X., Jeffers, J.R., Zambetti, G.P., and Xu, Y. (2012). Context-dependent enhancement of induced pluripotent stem cell reprogramming by silencing Puma. Stem Cells 2012Feb6. doi: 10.1002/stem.1054. [Epub ahead of print]10.1002/stem.105410.1002/stem.1054
[42] Laurent, L.C., Ulitsky, I., Slavin, I., Tran, H., Schork, A., Morey, R., Lynch, C., Harness, J.V., Lee, S., Barrero, M.J., . (2011). Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. Cell Stem Cell 8, 106-118 .10.1016/j.stem.2010.12.003
[43] Lee, G., Papapetrou, E.P., Kim, H., Chambers, S.M., Tomishima, M.J., Fasano, C.A., Ganat, Y.M., Menon, J., Shimizu, F., Viale, A., . (2009). Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461, 402-406 .10.1038/nature08320
[44] Levings, P.P.,McGarry, S.V., Currie, T.P., Nickerson, D.M., McClellan, S., Ghivizzani, S.C., Steindler, D.A., and Gibbs, C.P. (2009). Expression of an exogenous human Oct-4 promoter identifies tumor-initiating cells in osteosarcoma. Cancer Res 69, 5648-5655 .10.1158/0008-5472.CAN-08-3580
[45] Li, H., Collado, M., Villasante, A., Strati, K., Ortega, S., Canamero, M., Blasco, M.A., and Serrano, M. (2009a). The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460, 1136-1139 .10.1038/nature08290
[46] Li, W., Wei, W., Zhu, S., Zhu, J., Shi, Y., Lin, T., Hao, E., Hayek, A., Deng, H., and Ding, S. (2009b). Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors. Cell Stem Cell 4, 16-19 .10.1016/j.stem.2008.11.014
[47] Li, W., Zhou, H., Abujarour, R., Zhu, S., Young Joo, J., Lin, T., Hao, E., Sch?ler, H.R., Hayek, A., and Ding, S. (2009c). Generation of human-induced pluripotent stem cells in the absence of exogenous Sox2. Stem Cells 27, 2992-3000 .
[48] Li, Y., Zhang, Q., Yin, X., Yang, W., Du, Y., Hou, P., Ge, J., Liu, C., Zhang, W., Zhang, X., . (2011). Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules. Cell Res 21, 196-204 .10.1038/cr.2010.142
[49] Lin, T., Ambasudhan, R., Yuan, X., Li, W., Hilcove, S., Abujarour, R., Lin, X., Hahm, H.S., Hao, E., Hayek, A., . (2009). A chemical platform for improved induction of human iPSCs. Nat Methods 6, 805-808 .10.1038/nmeth.1393
[50] Lin, T., Chao, C., Saito, S., Mazur, S.J., Murphy, M.E., Appella, E., and Xu, Y. (2005). p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Biol 7, 165-171 .10.1038/ncb1211
[51] Lister, R., Pelizzola, M., Kida, Y.S., Hawkins, R.D., Nery, J.R., Hon, G., Antosiewicz-Bourget, J., O’Malley, R., Castanon, R., Klugman, S., . (2011). Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471, 68-73 .10.1038/nature09798
[52] Liu, G.H., Barkho, B.Z., Ruiz, S., Diep, D., Qu, J., Yang, S.L., Panopoulos, A.D., Suzuki, K., Kurian, L., Walsh, C., . (2011). Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472, 221-225 .10.1038/nature09879
[53] Liu, H., Zhu, F., Yong, J., Zhang, P., Hou, P., Li, H., Jiang, W., Cai, J., Liu, M., Cui, K., . (2008). Generation of induced pluripotent stem cells from adult rhesus monkey fibroblasts. Cell Stem Cell 3, 587-590 .10.1016/j.stem.2008.10.014
[54] Loh, Y.H., Wu, Q., Chew, J.L., Vega, V.B., Zhang, W., Chen, X., Bourque, G., George, J., Leong, B., Liu, J., . (2006). The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38, 431-440 .10.1038/ng1760
[55] Maherali, N., Ahfeldt, T., Rigamonti, A., Utikal, J., Cowan, C., and Hochedlinger, K. (2008). A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 3, 340-345 .10.1016/j.stem.2008.08.003
[56] Marchetto, M.C., Carromeu, C., Acab, A., Yu, D., Yeo, G.W., Mu, Y., Chen, G., Gage, F.H., and Muotri, A.R. (2010). A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143, 527-539 .10.1016/j.cell.2010.10.016
[57] Marión, R.M., Strati, K., Li, H., Murga, M., Blanco, R., Ortega, S., Fernandez-Capetillo, O., Serrano, M., and Blasco, M.A. (2009). A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460, 1149-1153 .10.1038/nature08287
[58] Masui, S., Nakatake, Y., Toyooka, Y., Shimosato, D., Yagi, R., Takahashi, K., Okochi, H., Okuda, A., Matoba, R., Sharov, A.A., . (2007). Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol 9, 625-635 .10.1038/ncb1589
[59] Mayshar, Y., Ben-David, U., Lavon, N., Biancotti, J.C., Yakir, B., Clark, A.T., Plath, K., Lowry, W.E., and Benvenisty, N. (2010). Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell 7, 521-531 .10.1016/j.stem.2010.07.017
[60] Mitsui, K., Tokuzawa, Y., Itoh, H., Segawa, K., Murakami, M., Takahashi, K., Maruyama, M., Maeda, M., and Yamanaka, S. (2003). The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113, 631-642 .10.1016/S0092-8674(03)00393-3
[61] Moretti, A., Bellin, M., Welling, A., Jung, C.B., Lam, J.T., Bott-Flügel, L., Dorn, T., Goedel, A., H?hnke, C., Hofmann, F., . (2010). Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl J Med 363, 1397-1409 .10.1056/NEJMoa0908679
[62] Newman, M.A., Thomson, J.M., and Hammond, S.M. (2008). Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA 14, 1539-1549 .10.1261/rna.1155108
[63] Nguyen, H.N., Byers, B., Cord, B., Shcheglovitov, A., Byrne, J., Gujar, P., Kee, K., Schüle, B., Dolmetsch, R.E., Langston, W., . (2011). LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell 8, 267-280 .10.1016/j.stem.2011.01.013
[64] Niwa, H., Miyazaki, J., and Smith, A.G. (2000). Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24, 372-376 .10.1038/74199
[65] Okita, K., Ichisaka, T., and Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature 448, 313-317 .10.1038/nature05934
[66] Park, I.H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., Lensch, M.W., Cowan, C., Hochedlinger, K., and Daley, G.Q. (2008a). Disease-specific induced pluripotent stem cells. Cell 134, 877-886 .10.1016/j.cell.2008.07.041
[67] Park, I.H., Zhao, R., West, J.A., Yabuuchi, A., Huo, H., Ince, T.A., Lerou, P.H., Lensch, M.W., and Daley, G.Q. (2008b). Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451, 141-146 .10.1038/nature06534
[68] Peng, S., Maihle, N.J., and Huang, Y. (2010). Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer. Oncogene 29, 2153-2159 .10.1038/onc.2009.500
[69] Pesce, M., and Sch?ler, H.R. (2001). Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells 19, 271-278 .10.1634/stemcells.19-4-271
[70] Pick, M., Stelzer, Y., Bar-Nur, O., Mayshar, Y., Eden, A., and Benvenisty, N. (2009). Clone- and gene-specific aberrations of parental imprinting in human induced pluripotent stem cells. Stem Cells 27, 2686-2690 .10.1002/stem.205
[71] Piestun, D., Kochupurakkal, B.S., Jacob-Hirsch, J., Zeligson, S., Koudritsky, M., Domany, E., Amariglio, N., Rechavi, G., and Givol, D. (2006). Nanog transforms NIH3T3 cells and targets cell-type restricted genes. Biochem Biophys Res Commun 343, 279-285 .10.1016/j.bbrc.2006.02.152
[72] Polo, J.M., Liu, S., Figueroa, M.E., Kulalert, W., Eminli, S., Tan, K.Y., Apostolou, E., Stadtfeld, M., Li, Y., Shioda, T., . (2010). Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol 28, 848-855 .10.1038/nbt.1667
[73] Rowland, B.D., and Peeper, D.S. (2006). KLF4, p21 and context-dependent opposing forces in cancer. Nat Rev Cancer 6, 11-23 .10.1038/nrc1780
[74] Sarig, R., Rivlin, N., Brosh, R., Bornstein, C., Kamer, I., Ezra, O., Molchadsky, A., Goldfinger, N., Brenner, O., and Rotter, V. (2010). Mutant p53 facilitates somatic cell reprogramming and augments the malignant potential of reprogrammed cells. J Exp Med 207, 2127-2140 .10.1084/jem.20100797
[75] Shi, Y., Desponts, C., Do, J.T., Hahm, H.S., Sch?ler, H.R., and Ding, S. (2008). Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell 3, 568-574 .10.1016/j.stem.2008.10.004
[76] Song, H., Chung, S.K., and Xu, Y. (2010). Modeling disease in human ESCs using an efficient BAC-based homologous recombination system. Cell Stem Cell 6, 80-89 .10.1016/j.stem.2009.11.016
[77] Stadtfeld, M., Apostolou, E., Akutsu, H., Fukuda, A., Follett, P., Natesan, S., Kono, T., Shioda, T., and Hochedlinger, K. (2010). Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature 465, 175-181 .10.1038/nature09017
[78] Stadtfeld, M., Brennand, K., and Hochedlinger, K. (2008). Reprogramming of pancreatic beta cells into induced pluripotent stem cells. Curr Biol 18, 890-894 .10.1016/j.cub.2008.05.010
[79] Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., and Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872 .10.1016/j.cell.2007.11.019
[80] Takahashi, K., and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676 .10.1016/j.cell.2006.07.024
[81] Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S., and Jones, J.M. (1998). Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147 .10.1126/science.282.5391.1145
[82] Tiscornia, G., Vivas, E.L., and Belmonte, J.C. (2011). Diseases in a dish: modeling human genetic disorders using induced pluripotent cells. Nat Med 17, 1570-1576 .10.1038/nm.2504
[83] Tong, M., Lv, Z., Liu, L., Zhu, H., Zheng, Q.Y., Zhao, X.Y., Li, W., Wu, Y.B., Zhang, H.J., Wu, H.J., . (2011). Mice generated from tetraploid complementation competent iPS cells show similar developmental features as those from ES cells but are prone to tumorigenesis. Cell Res 21, 1634-1637 .10.1038/cr.2011.143
[84] Utikal, J., Maherali, N., Kulalert, W., and 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 .10.1242/jcs.054783
[85] Utikal, J., Polo, J.M., Stadtfeld, M., Maherali, N., Kulalert, W., Walsh, R.M., Khalil, A., Rheinwald, J.G., and Hochedlinger, K. (2009b). Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460, 1145-1148 10.1038/nature08285
[86] Viswanathan, S.R., Daley, G.Q., and Gregory, R.I. (2008). Selective blockade of microRNA processing by Lin28. Science 320, 97-100 .10.1126/science.1154040
[87] 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., . (2009). Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet 41, 843-848 .10.1038/ng.392
[88] Wu, Y., Zhang, Y., Mishra, A., Tardif, S.D., and Hornsby, P.J. (2010). Generation of induced pluripotent stem cells from newborn marmoset skin fibroblasts. Stem Cell Res 4, 180-188 .10.1016/j.scr.2010.02.003
[89] Yamanaka, S. (2007). Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell 1, 39-49 .10.1016/j.stem.2007.05.012
[90] Yazawa, M., Hsueh, B., Jia, X., Pasca, A.M., Bernstein, J.A., Hallmayer, J., and Dolmetsch, R.E. (2011). Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature 471, 230-234 .10.1038/nature09855
[91] 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., . (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917-1920 .10.1126/science.1151526
[92] Yuan, X., Wan, H., Zhao, X., Zhu, S., Zhou, Q., and Ding, S. (2011). Combined chemical treatment enables Oct4-induced reprogramming from mouse embryonic fibroblasts. Stem Cells 29, 549-553 .10.1002/stem.594
[93] Zhang, J., Lian, Q., Zhu, G., Zhou, F., Sui, L., Tan, C., Mutalif, R.A., Navasankari, R., Zhang, Y., Tse, H.F., . (2011). A human iPSC model of Hutchinson Gilford Progeria reveals vascular smooth muscle and mesenchymal stem cell defects. Cell Stem Cell 8, 31-45 .10.1016/j.stem.2010.12.002
[94] Zhao, T., and Xu, Y. (2010). p53 and stem cells: new developments and new concerns. Trends Cell Biol 20, 170-175 .10.1016/j.tcb.2009.12.004
[95] Zhao, T., Zhang, Z.N., Rong, Z., and Xu, Y. (2011). Immunogenicity of induced pluripotent stem cells. Nature 474, 212-215 .
[96] Zhao, X.Y., Li, W., Lv, Z., Liu, L., Tong, M., Hai, T., Hao, J., Guo, C.L., Ma, Q.W., Wang, L., . (2009). iPS cells produce viable mice through tetraploid complementation. Nature 461, 86-90 .10.1038/nature08267
[97] Zhao, Y., Yin, X., Qin, H., Zhu, F., Liu, H., Yang, W., Zhang, Q., Xiang, C., Hou, P., Song, Z., . (2008). Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell 3, 475-479 .10.1016/j.stem.2008.10.002
[98] Zhu, S., Li, W., Zhou, H., Wei, W., Ambasudhan, R., Lin, T., Kim, J., Zhang, K., and Ding, S. (2010). Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell 7, 651-655 .10.1016/j.stem.2010.11.015
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