Induced pluripotency and epigenetic reprogramming

Cold Spring Harbor Perspectives in Biology

Volumn 7, Issue 12, 2015, Pages

  Hochedlinger, Konrad ^a   Jaenisch, Rudolf ^b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSCRIPTION FACTOR;

ANIMAL; CELL CULTURE TECHNIQUE; CELL DEDIFFERENTIATION; CELL LINE; CELL NUCLEUS TRANSPLANTATION; CLONING; EMBRYONIC STEM CELL; FEMALE; GENETIC EPIGENESIS; HUMAN; INDUCED PLURIPOTENT STEM CELL; MARKOV CHAIN; MOUSE; PHYSIOLOGY; X CHROMOSOME INACTIVATION;

ANIMALS; CELL CULTURE TECHNIQUES; CELL DEDIFFERENTIATION; CELL LINE; CLONING, ORGANISM; EMBRYONIC STEM CELLS; EPIGENESIS, GENETIC; FEMALE; HUMANS; INDUCED PLURIPOTENT STEM CELLS; MICE; NUCLEAR TRANSFER TECHNIQUES; STOCHASTIC PROCESSES; TRANSCRIPTION FACTORS; X CHROMOSOME INACTIVATION;

EID: 84949199803     PISSN: None     EISSN: 19430264     Source Type: Journal    
DOI: 10.1101/cshperspect.a019448     Document Type: Article

References (170)

1. Aasen T, Raya A, Barrero MJ, Garreta E, Consiglio A, Gonzalez F, Vassena R, Bilic J, Pekarik V, Tiscornia G, et al. 2008. Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol 26: 1276–1284.
2. Ang YS, Tsai SY, Lee DF, Monk J, Su J, Ratnakumar K, Ding J, Ge Y, Darr H, Chang B, et al. 2011. Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell 145: 183–197.
3. Anguera MC, Sadreyev R, Zhang Z, Szanto A, Payer B, Sheridan SD, Kwok S, Haggarty SJ, Sur M, Alvarez J, et al. 2012. Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes. Cell Stem Cell 11: 75–90.
4. 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.
5. Augui S, Nora EP, Heard E. 2011. Regulation of X-chromosome inactivation by the X-inactivation centre. Nat Rev Genet 12: 429–442.
6. Banito A, Rashid ST, Acosta JC, Li S, Pereira CF, Geti I, Pinho S, Silva JC, Azuara V, Walsh M, et al. 2009. Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev 23: 2134–2139.
7. Baylin SB, Jones PA. 2014. Epigenetic determinants of cancer. Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a019505.
8. Blelloch R, Venere M, Yen J, Ramalho-Santos M. 2007. Generation of induced pluripotent stem cells in the absence of drug selection. Cell Stem Cell 1: 245–247.
9. Bock C, Kiskinis E, Verstappen G, Gu H, Boulting G, Smith ZD, Ziller M, Croft GF, Amoroso MW, Oakley DH, et al. 2011. Reference maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell 144: 439–452.
10. Bogdanove AJ, Voytas DF. 2011. TAL effectors: Customizable proteins for DNA targeting. Science 333: 1843–1846.
11. Boland MJ, Hazen JL, Nazor KL, Rodriguez AR, Gifford W, Martin G, Kupriyanov S, Baldwin KK. 2009. Adult mice generated from induced pluripotent stem cells. Nature 461: 91–94.
12. Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, Levine SS, Wernig M, Tajonar A, Ray MK, et al. 2006. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441: 349–353.
13. Brambrink T, Hochedlinger K, Bell G, Jaenisch R. 2006. ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable. Proc Natl Acad Sci 103: 933–938.
14. Brambrink T, Foreman R, Welstead GG, Lengner CJ, Wernig M, Suh H, Jaenisch R. 2008. Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell 2: 151–159.
15. Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, Li Y, Mu Y, Chen G, Yu D, et al. 2011. Modelling schizophrenia using human induced pluripotent stem cells. Nature 473: 221–225.
16. Briggs R, King TJ. 1952. Transplantation of living nuclei from blastula cells into enucleated frogs’ eggs. Proc Natl Acad Sci 38: 455–463.
17. Briggs R, King TJ. 1957. Changes in the nuclei of differentiating endoderm cells as revealed by nuclear transplantation. J Morphol 100: 269–311.
18. Brockdorff N, Turner BM. 2014. Dosage compensation in mammals. Cold Spring Harb Perspect Biol doi: 10.1101/cshperspect.a019406.
19. Brons IG, Smithers LE, Trotter MW, Rugg-Gunn P, Sun B, Howlett SK, Clarkson A, Ahrlund-Richter L, Pedersen RA, et al. 2007. Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448: 191–195.
20. Bussmann LH, Schubert A, Vu Manh TP, De Andres L, Desbordes SC, Parra M, Zimmermann T, Rapino F, Rodriguez-Ubreva J, Ballestar E, et al. 2009. A robust and highly efficient immune cell reprogramming system. Cell Stem Cell 5: 554–566.
21. Carey BW, Markoulaki S, Beard C, Hanna J, Jaenisch R. 2010. Single-gene transgenic mouse strains for reprogramming adult somatic cells. Nat Methods 7: 56–59.
22. Carey BW, Markoulaki S, Hanna JH, Faddah DA, Buganim Y, Kim J, Ganz K, Steine EJ, Cassady JP, Creyghton MP, et al. 2011. Reprogramming factor stoichiometry influences the epigenetic state and biological properties of induced pluripotent stem cells. Cell Stem Cell 9: 588–598.
23. Carvajal-Vergara X, Sevilla A, D’Souza SL, Ang YS, Schaniel C, Lee DF, Yang L, Kaplan AD, Adler ED, Rozov R, et al. 2010. Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 465: 808–812.
24. Chambers I, Smith A. 2004. Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23: 7150–7160.
25. Chen J, Liu J, Yang J, Chen Y, Chen J, Ni S, Song H, Zeng L, Ding K, Pei D. 2011. BMPs functionally replace Klf4 and support efficient reprogramming of mouse fibroblasts by Oct4 alone. Cell Res 21: 205–212.
26. Cheng L, Hansen NF, Zhao L, Du Y, Zou C, Donovan FX, Chou BK, Zhou G, Li S, Dowey SN, et al. 2012. Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by nonintegrating plasmid expression. Cell Stem Cell 10: 337–344.
27. Chin MH, Mason MJ, Xie W, Volinia S, Singer M, Peterson C, Ambartsumyan G, Aimiuwu O, Richter L, Zhang J, et al. 2009. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 5: 111–123.
28. Collado M, Blasco MA, Serrano M. 2007. Cellular senescence in cancer and aging. Cell 130: 223–233.
29. Daley GQ. 2012. The promise and perils of stem cell therapeutics. Cell Stem Cell 10: 740–749.
30. Davis RL, Weintraub H, Lassar AB. 1987. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51: 987–1000.
31. Ebert AD, Yu J, Rose FF Jr, Mattis VB, Lorson CL, Thomson JA, Svendsen CN. 2009. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457: 277–280.
32. Eggan K, Akutsu H, Hochedlinger K, Rideout W, Yanagimachi R, Jaenisch R. 2000. X-chromosome inactivation in cloned mouse embryos. Science 290: 1578–1581.
33. Eggan K, Akutsu H, Loring J, Jackson-Grusby L, Klemm M, Rideout WM, Yanagimachi R, Jaenisch R. 2001. Hybrid vigor, fetal overgrowth, and viability of mice derived by nuclear cloning and tetraploid embryo complementation. Proc Natl Acad Sci 98: 6209–6214.
34. Eggan K, Baldwin K, Tackett M, Osborne J, Gogos J, Chess A, Axel R, Jaenisch R. 2004. Mice cloned from olfactory sensory neurons. Nature 428: 44–49.
35. 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.
36. Eminli S, Foudi A, Stadtfeld M, Maherali N, Ahfeldt T, Mostoslavsky G, Hock H, Hochedlinger K. 2009. Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat Genet 41: 968–976.
37. Evans MJ, Kaufman MH. 1981. Establishment in culture of pluripotential cells from mouse embryos. Nature 292: 154–156.
38. Feng B, Jiang J, Kraus P, Ng JH, Heng JC, Chan YS, Yaw LP, Zhang W, Loh YH, Han J, et al. 2009. Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat Cell Biol 11: 197–203.
39. Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M. 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: 348–362.
40. Gaspar-Maia A, Alajem A, Polesso F, Sridharan R, Mason MJ, Heidersbach A, Ramalho-Santos J, McManus MT, Plath K, Meshorer E, et al.2009. Chd1 regulates open chromatin and pluripotency of embryonic stem cells. Nature 460: 863–868.
41. Gore A, Li Z, Fung HL, Young JE, Agarwal S, Antosiewicz-Bourget J, Canto I, Giorgetti A, Israel MA, Kiskinis E, et al. 2011. Somatic coding mutations in human induced pluripotent stem cells. Nature 471: 63–67.
42. Guenther MG, Frampton GM, Soldner F, Hockemeyer D, Mitalipova M, Jaenisch R, Young RA. 2010. Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells. Cell Stem Cell 7: 249–257.
43. Guo G, Yang J, Nichols J, Hall JS, Eyres I, Mansfield W, Smith A. 2009. Klf4 reverts developmentally programmed restriction of ground state pluripotency. Development 136: 1063–1069.
44. Gurdon J. 1962. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 10: 622–640.
45. Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, et al. 2007. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318: 1920–1923.
46. Hanna J, Carey BW, Jaenisch R. 2008a. Reprogramming of somatic cell identity. Cold Spring Harb Symp Quant Biol 73: 147–155.
47. Hanna J, Markoulaki S, Schorderet P, Carey BW, Beard C, Wernig M, Creyghton MP, Steine EJ, Cassady JP, Foreman R, et al. 2008b. Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 133: 250–264.
48. Hanna J, Markoulaki S, Mitalipova M, Cheng AW, Cassady JP, Staerk J, Carey BW, Lengner CJ, Foreman R, Love J, et al. 2009a. Metastable pluripotent states in NOD-mouse-derived ESCs. Cell Stem Cell 4: 513–524.
49. Hanna J, Saha K, Pando B, van Zon J, Lengner CJ, Creyghton MP, van Oudenaarden A, Jaenisch R. 2009b. Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462: 595–601.
50. Hanna J, Cheng AW, Saha K, Kim J, Lengner CJ, Soldner F, Cassady JP, Muffat J, Carey BW, Jaenisch R. 2010a. Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proc Natl Acad Sci 107: 9222–9227.
51. Hanna JH, Saha K, Jaenisch R. 2010b. Pluripotency and cellular reprogramming: Facts, hypotheses, unresolved issues. Cell 143: 508–525.
52. Heng JC, Feng B, Han J, Jiang J, Kraus P, Ng JH, Orlov YL, Huss M, Yang L, Lufkin T, et al. 2010. The nuclear receptor Nr5a2 can replace Oct4 in the reprogramming of murine somatic cells to pluripotent cells. Cell Stem Cell 6: 167–174.
53. Hochedlinger K, Jaenisch R. 2002. Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature 415: 1035–1038.
54. Hochedlinger K, Jaenisch R. 2003. Nuclear transplantation, embryonic stem cells, and the potential for cell therapy. N Engl J Med 5: S114–S117.
55. Hockemeyer D, Soldner F, Cook EG, Gao Q, Mitalipova M, Jaenisch R. 2008. A drug-inducible system for direct reprogramming of human somatic cells to pluripotency. Cell Stem Cell 3: 346–353.
56. Hockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, DeKelver RC, Katibah GE, Amora R, Boydston EA, Zeitler B, et al. 2009. Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol 27: 851–857.
57. Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ, Zhang L, Santiago Y, Miller JC, et al. 2011. Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29: 731–734.
58. 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.
59. Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, Zhao T, Ye J, Yang W, Liu K, et al. 2013. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 341: 651–654.
60. Huang P, He Z, Ji S, Sun H, Xiang D, Liu C, Hu Y, Wang X, Hui L. 2011. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 475: 386–389.
61. Huangfu D, Maehr R, Guo W, Eijkelenboom A, Snitow M, Chen AE, Melton DA. 2008. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26: 795–797.
62. Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Narva E, Ng S, Sourour M, Hamalainen R, Olsson C, et al. 2011. Copy number variation and selection during reprogramming to pluripotency. Nature 471: 58–62.
63. Ichida JK, Blanchard J, Lam K, Son EY, Chung JE, Egli D, Loh KM, Carter AC, Di Giorgio FP, Koszka K, et al. 2009. A small-molecule inhibitor of tgf-b signaling replaces sox2 in reprogramming by inducing nanog. Cell Stem Cell 5: 491–503.
64. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D. 2010. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142: 375–386.
65. Inoue K, Wakao H, Ogonuki N, Miki H, Seino K, Nambu-Wakao R, Noda S, Miyoshi H, Koseki H, Taniguchi M, et al. 2005. Generation of cloned mice by direct nuclear transfer from natural killer T cells. Curr Biol 15: 1114–1118.
66. Jaenisch R, Gurdon J. 2007. Nuclear transplantation and the reprogramming of the genome. In Epigenetics ed. Allis CD, et al. 415–434. Cold Spring Harbor Laboratory Press
67. Harbor NY, Jaenisch R, Young R. 2008. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 132: 567–582.
68. Jiang J, Chan YS, Loh YH, Cai J, Tong GQ, Lim CA, Robson P, Zhong S, Ng HH. 2008. A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol 10: 353–360.
69. Kaji K, Caballero IM, MacLeod R, Nichols J, Wilson VA, Hendrich B. 2006. The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. Nat Cell Biol 8: 285–292.
70. Kang L, Wang J, Zhang Y, Kou Z, Gao S. 2009. iPS cells can support fullterm development of tetraploid blastocyst-complemented embryos. Cell Stem Cell 5: 135–138.
71. Kawamura T, Suzuki J, Wang YV, Menendez S, Morera LB, Raya A, Wahl GM, Izpisua Belmonte JC. 2009. Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460: 1140–1144.
72. Kelly SJ. 1977. Studies of the developmental potential of 4- and 8-cell stage mouse blastomeres. J Exp Zool 200: 365–376.
73. Kim JB, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, Arauzo-Bravo MJ, Ruau D, Han DW, Zenke M, et al. 2008. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 454: 646–650.
74. Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, et al. 2009a. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4: 472–476.
75. Kim HH, Kuwano Y, Srikantan S, Lee EK, Martindale JL, Gorospe M. 2009b. HuR recruits let-7/RISC to repress c-Myc expression. Genes Dev 23: 1743–1748.
76. Kim K, Doi
77. Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji H, Ehrlich LI, et al. 2010. Epigenetic memory in induced pluripotent stem cells. Nature 467: 285–290.
78. Kleinsmith LJ, Pierce GB Jr. 1964. Multipotentiality of single embryonal carcinoma cells. Cancer Res 24: 1544–1551.
79. Knoepfler PS. 2008.Why myc? An unexpected ingredient in the stem cell cocktail. Cell Stem Cell 2: 18–21.
80. Laiosa CV, Stadtfeld M, Xie H, de Andres-Aguayo L, Graf T. 2006. Reprogramming of committed T cell progenitors to macrophages and dendritic cells by C/EBP a and PU.1 transcription factors. Immunity 25: 731–744.
81. Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, Chevalier B, Johnstone SE, Cole MF, Isono K, et al. 2006. Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 125: 301–313.
82. Lee G, Papapetrou EP, Kim H, Chambers SM, Tomishima MJ, Fasano CA, Ganat YM, Menon J, Shimizu F, Viale A, et al. 2009. Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461: 402–406.
83. Lei H, Oh SP, Okano M, Juttermann R, Goss KA, Jaenisch R, Li E. 1996. De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development 122: 3195–3205.
84. Lengner CJ, Gimelbrant AA, Erwin JA, Cheng AW, Guenther MG, Welstead GG, Alagappan R, Frampton GM, Xu P, Muffat J, et al. 2010. Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell 141: 872–883.
85. Li E, Bestor TH, Jaenisch R. 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69: 915–926.
86. Li H, Collado M, Villasante A, Strati K, Ortega S, Canamero M, Blasco MA, Serrano M. 2009a. The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460: 1136–1139.
87. Li W, Wei W, Zhu S, Zhu J, Shi Y, Lin T, Hao E, Hayek A, Deng H, 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.
88. Li R, Liang J, Ni S, Zhou T, Qing X, Li H, He W, Chen J, Li F, Zhuang Q, et al. 2010. A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell 7: 51–63.
89. Lin CH, Lin C, Tanaka H, Fero ML, Eisenman RN. 2009. Gene regulation and epigenetic remodeling in murine embryonic stem cells by c-Myc. PloS One 4: e7839.
90. Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, Antosiewicz- Bourget J, O’Malley R, Castanon R, Klugman S, et al. 2011. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471: 68–73.
91. Liu H, Zhu F, Yong J, Zhang P, Hou P, Li H, Jiang W, Cai J, Liu M, Cui K, etal. 2008. Generation of induced pluripotent stem cells from adult rhesus monkey fibroblasts. Cell Stem Cell 3: 587–590.
92. Lyssiotis CA, Foreman RK, Staerk J, Garcia M, Mathur D, Markoulaki S, Hanna J, Lairson LL, Charette BD, Bouchez LC, et al. 2009.Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4. ProcNatlAcad Sci 106: 8912–8917.
93. Maekawa M, Yamaguchi K, Nakamura T, Shibukawa R, Kodanaka I, Ichisaka T, Kawamura Y, Mochizuki H, Goshima N, Yamanaka S. 2011. Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Nature 474: 225–229.
94. Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, et al. 2007. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1: 55–70.
95. Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K. 2008. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 3: 340–345.
96. Mansour AA, Gafni O, Weinberger L, Zviran A, Ayyash M, Rais Y, Krupalnik V, Zerbib M, Amann-Zalcenstein D, Maza I, et al. 2012. The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming. Nature 488: 409–413.
97. Marchetto MC, Carromeu C, Acab A, YuD, YeoGW,Mu Y, Chen G, Gage FH,Muotri AR. 2010. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143: 527–539.
98. Marion RM, Strati K, Li H, Tejera A, Schoeftner S, Ortega S, Serrano M, Blasco MA. 2009. Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell 4: 141–154.
99. Markoulaki S, Hanna J, Beard C, Carey BW, Cheng AW, Lengner CJ, Dausman JA, Fu D, Gao Q, Wu S, et al. 2009. Transgenic mice with defined combinations of drug-inducible reprogramming factors. Nat Biotechnol 27: 169–171.
100. Martin GR. 1981. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci 78: 7634–7638.
101. Matsui T, Leung D, Miyashita H, Maksakova IA, Miyachi H, Kimura H, Tachibana M, Lorincz MC, Shinkai Y. 2010. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature 464: 927–931.
102. Meissner A, Jaenisch R. 2006. Mammalian nuclear transfer. DevDyn 235: 2460–2469.
103. Meissner A, Wernig M, Jaenisch R. 2007. Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol 25: 1177–1181.
104. Mekhoubad S, Bock C, de Boer AS, Kiskinis E, Meissner A, Eggan K. 2012. Erosion of dosage compensation impacts human iPSC disease modeling. Cell Stem Cell 10: 595–609.
105. Mikkelsen TS, Hanna J, Zhang X, Ku M, Wernig M, Schorderet P, Bernstein BE, Jaenisch R, Lander ES, Meissner A. 2008. Dissecting direct reprogramming through integrative genomic analysis. Nature 454: 49–55.
106. Miller RA, Ruddle FH. 1976. Pluripotent teratocarcinoma-thymus somatic cell hybrids. Cell 9: 45–55.
107. Munsie MJ, Michalska AE, O’Brien CM, Trounson AO, Pera MF, Mountford PS. 2000. Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei. Curr Biol 10: 989–992.
108. Nagy A, Gocza E, Diaz EM, Prideaux VR, Ivanyi E, Markkula M, Rossant J. 1990. Embryonic stem cells alone are able to support fetal development in the mouse. Development 110: 815–821.
109. 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.
110. Nakagawa M, Takizawa N, Narita M, Ichisaka T, Yamanaka S. 2010. Promotion of direct reprogramming by transformation-deficient Myc. Proc Natl Acad Sci 107: 14152–14157.
111. Nemajerova A, Kim SY, Petrenko
112. O, Moll UM. 2012. Two-factor reprogramming of somatic cells to pluripotent stem cells reveals partial functional redundancy of Sox2 and Klf4. Cell Death Differ 19: 1268–1276.
113. Newman AM, Cooper JB. 2010. Lab-specific gene expression signatures in pluripotent stem cells. Cell Stem Cell 7: 258–262.
114. Nichols J, Smith A. 2009. Naive and primed pluripotent states. Cell Stem Cell 4: 487–492.
115. Ohi Y, Qin H, Hong C, Blouin L, Polo JM, Guo T, Qi Z, Downey SL, Manos PD, Rossi DJ, et al. 2011. Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells. Nat Cell Biol 13: 541–549.
116. Okamoto I, Patrat C, Thepot D, Peynot N, Fauque P, Daniel N, Diabangouaya P, Wolf JP, Renard JP, Duranthon V, et al. 2011. Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development. Nature 472: 370–374.
117. Okita K, Ichisaka T, Yamanaka S. 2007. Generation of germline-competent induced pluripotent stem cells. Nature 448: 313–317.
118. Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. 2008. Generation of mouse induced pluripotent stem cells without viral vectors. Science 322: 949–953.
119. Orkin SH, Hochedlinger K. 2011. Chromatin connections to pluripotency and cellular reprogramming. Cell 145: 835–850.
120. Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ. 2008. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451: 141–146.
121. Pawlak M, Jaenisch R. 2011. De novo DNA methylation by Dnmt3a and Dnmt3b is dispensable for nuclear reprogramming of somatic cells to a pluripotent state. Genes Dev 25: 1035–1040.
122. Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, Apostolou E, Stadtfeld M, Li Y, Shioda T, et al. 2010. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol 28: 848–855.
123. Raya A, Rodriguez-Piza I, Guenechea G, Vassena R, Navarro S, Barrero MJ, Consiglio A, Castella M, Rio P, Sleep E, et al. 2009. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 460: 53–59.
124. Reik W, Dean W, Walter J. 2001. Epigenetic reprogramming in mammalian development. Science 293: 1089–1093.
125. Rubin LL. 2008. Stem cells and drug discovery: The beginning of a new era? Cell 132: 549–552.
126. Samavarchi-Tehrani P, Golipour A, David L, Sung HK, Beyer TA, Datti A, Woltjen K, Nagy A, Wrana JL. 2010. Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. Cell Stem Cell 7: 64–77.
127. Shen Y, Matsuno Y, Fouse SD, Rao N, Root S, Xu R, Pellegrini M, Riggs AD, Fan G. 2008. X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations. Proc Natl Acad Sci 105: 4709–4714.
128. Singhal N, Graumann J, Wu G, Arauzo-Bravo MJ, Han DW, Greber B, Gentile L, Mann M, Scholer HR. 2010. Chromatin-remodeling components of the BAF complex facilitate reprogramming. Cell 141: 943–955.
129. Smith ZD, Nachman I, Regev A, Meissner A. 2010. Dynamic single-cell imaging of direct reprogramming reveals an early specifying event. Nat Biotechnol 28: 521–526.
130. Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, et al. 2009. Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136: 964–977.
131. Soldner F, Laganiere J, Cheng AW, Hockemeyer D, Gao Q, Alagappan R, Khurana V, Golbe LI, Myers RH, Lindquist S, et al. 2011. Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell 146: 318–331.
132. Sridharan R, Tchieu J, Mason MJ, 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.
133. Stadtfeld M, Hochedlinger K. 2010. Induced pluripotency: History, mechanisms, and applications. Genes Dev 24: 2239–2263.
134. Stadtfeld M, Brennand K, Hochedlinger K. 2008a. Reprogramming of pancreatic b cells into induced pluripotent stem cells. Curr Biol 18: 890–894.
135. Stadtfeld M, Maherali N, Breault DT, Hochedlinger K. 2008b. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2: 230–240.
136. Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. 2008c. Induced pluripotent stem cells generated without viral integration. Science 322: 945–949.
137. Stadtfeld M, Apostolou E, Akutsu H, Fukuda A, Follett P, Natesan S, Kono T, Shioda T, Hochedlinger K. 2010a. Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature 465: 175–181.
138. Stadtfeld M, Maherali N, Borkent M, Hochedlinger K. 2010b. A reprogrammable mouse strain from gene-targeted embryonic stem cells. Nat Methods 7: 53–55.
139. Stadtfeld M, Apostolou E, Ferrari F, Choi J, Walsh RM, Chen T, Ooi SS, Kim SY, Bestor TH, Shioda T, et al. 2012. Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells. Nat Genet 44: 398–405, S391–S392.
140. Tachibana M, Amato P, Sparman M, Gutierrez NM, Tippner-Hedges R, Ma H, Kang E, Fulati A, Lee HS, Sritanaudomchai H, et al. 2013. Human embryonic stem cells derived by somatic cell nuclear transfer. Cell 153: 1228–1238.
141. Tada M, Morizane A, Kimura H, Kawasaki H, Ainscough JF, Sasai Y, Nakatsuji N, Tada T. 2003. Pluripotency of reprogrammed somatic genomes in embryonic stem hybrid cells. Dev Dyn 227: 504–510.
142. Takahashi K. 2014. Cellular reprogramming. Cold Spring Harb Persp Biol 6: a018606.
143. Takahashi K, Yamanaka S. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663–676.
144. 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.
145. Tesar PJ, Chenoweth JG, Brook FA, Davies TJ, Evans EP, Mack DL, Gardner RL, McKay RD. 2007.Newcell lines frommouse epiblast share defining features with human embryonic stem cells. Nature 448: 196–199.
146. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. 1998. Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147.
147. Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD. 2010. Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11: 636–646.
148. 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.
149. Utikal J, Polo JM, Stadtfeld M, Maherali N, Kulalert W, Walsh RM, Khalil A, Rheinwald JG, Hochedlinger K. 2009b. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460: 1145–1148.
150. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M. 2010. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463: 1035–1041.Viswanathan SR, Daley GQ, Gregory RI. 2008. Selective blockade of microRNA processing by Lin28. Science 320: 97–100.
151. Wakayama T, Tabar V, Rodriguez I, Perry AC, Studer L, Mombaerts P. 2001. Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science 292
152. 740–743.
153. Wakayama S, Jakt ML, Suzuki M, Araki R, Hikichi T, Kishigami S, Ohta H, Van Thuan N, Mizutani E, Sakaide Y, et al. 2006. Equivalency of nuclear transfer-derived embryonic stem cells to those derived from fertilized mouse blastocysts. Stem Cells 24: 2023–2033.
154. Wang J, Rao S, Chu J, Shen X, Levasseur DN, Theunissen TW, Orkin SH. 2006. A protein interaction network for pluripotency of embryonic stem cells. Nature 444: 364–368.
155. Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, et al. 2010. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7: 618–630.
156. Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R. 2007. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448: 318–324.
157. Wernig M, Lengner CJ, Hanna J, Lodato MA, Steine E, Foreman R, Staerk J, Markoulaki S, Jaenisch R. 2008. A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nat Biotechnol 26: 916–924.
158. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. 1997. Viable offspring derived from fetal and adult mammalian cells. Nature 385: 810–813.
159. Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hamalainen R, Cowling R, Wang W, Liu P, Gertsenstein M, et al. 2009. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458: 766–770.
160. Wu SM, Hochedlinger K. 2011. Harnessing the potential of induced pluripotent stem cells for regenerative medicine. Nat Cell Biol 13: 497–505.
161. Wutz A. 2012. Epigenetic alterations in human pluripotent stem cells: A tale of two cultures. Cell Stem Cell 11: 9–15.
162. Xie H, Ye M, Feng R, Graf T. 2004. Stepwise reprogramming of B cells into macrophages. Cell 117: 663–676.
163. Xu Y, Shi Y, Ding S. 2008. A chemical approach to stem-cell biology and regenerative medicine. Nature 453: 338–344.
164. Yamanaka S. 2009. Elite and stochastic models for induced pluripotent stem cell generation. Nature 460: 49–52.
165. Yamanaka S, Blau HM. 2010. Nuclear reprogramming to a pluripotent state by three approaches. Nature 465: 704–712.
166. Young MA, Larson DE, Sun CW, George DR, Ding L, Miller CA, Lin L, Pawlik KM, Chen K, Fan X, et al. 2012. Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells. Cell Stem Cell 10: 570–582.
167. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, et al. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318: 1917–1920.
168. Zhao XY, Li W, Lv Z, Liu L, Tong M, Hai T, Hao J, Guo CL, Ma QW, Wang L, et al. 2009. iPS cells produce viable mice through tetraploid complementation. Nature 461: 86–90.
169. Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. 2008. In vivo reprogramming of adult pancreatic exocrine cells to b-cells. Nature 455: 627–632.
170. Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y, et al. 2009. Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4: 381–384.