Science in China Series C: Life Sciences

, Volume 52, Issue 7, pp 622–636 | Cite as

Current progress and prospects of induced pluripotent stem cells

Special Topic Review
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Abstract

Induced pluripotent stem (iPS) cells are derived from somatic cells by ectopic expression of few transcription factors. Like embryonic stem (ES) cells, iPS cells are able to self-renew indefinitely and to differentiate into all types of cells in the body. iPS cells hold great promise for regenerative medicine, because iPS cells circumvent not only immunological rejection but also ethical issues. Since the first report on the derivation of iPS cells in 2006, many laboratories all over the world started research on iPS cells and have made significant progress. This paper reviews recent progress in iPS cell research, including the methods to generate iPS cells, the molecular mechanism of reprogramming in the formation of iPS cells, and the potential applications of iPS cells in cell replacement therapy. Current problems that need to be addressed and the prospects for iPS research are also discussed.

Keywords

induced pluripotent stem (iPS) cells somatic cell reprogramming pluripotency 
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References

  1. 1.
    Nagy A, Gócza E, Diaz E M, et al. Embryonic stem cells alone are able to support fetal development in the mouse. Development, 1990, 110: 815–821, 2088722, 1:STN:280:DyaK3M3gvFaguw%3D%3DPubMedGoogle Scholar
  2. 2.
    Poueymirou W T, Auerbach W, Frendewey D, et al. F0 generation mice fully derived from gene-targeted embryonic stem cells allowing immediate phenotypic analyses. Nat Biotechnol, 2007, 25: 91–99, 17187059, 10.1038/nbt1263, 1:CAS:528:DC%2BD2sXis1Gkuw%3D%3DPubMedCrossRefGoogle Scholar
  3. 3.
    Huang J, Deng K, Wu H, et al. Efficient production of mice from embryonic stem cells injected into four- or eight-cell embryos by piezo micromanipulation. Stem Cells, 2008, 26: 1883–1890, 18467666, 10.1634/stemcells.2008-0164, 1:CAS:528:DC%2BD1cXpvV2lsr0%3DPubMedCrossRefGoogle Scholar
  4. 4.
    Evans M J, Kaufman M H. Establishment in culture of pluripotential cells from mouse embryos. Nature, 1981, 292: 154–156, 7242681, 10.1038/292154a0, 1:STN:280:DyaL3M3itV2qsg%3D%3DPubMedCrossRefGoogle Scholar
  5. 5.
    Martin G R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA, 1981, 78: 7634–7638, 6950406, 10.1073/pnas.78.12.7634, 1:STN:280:DyaL387ltV2htg%3D%3DPubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Kim K, Lerou P, Yabuuchi A, et al. Histocompatible embryonic stem cells by parthenogenesis. Science, 2007, 315: 482–486, 17170255, 10.1126/science.1133542, 1:CAS:528:DC%2BD2sXotFCiuw%3D%3DPubMedCrossRefGoogle Scholar
  7. 7.
    Munsie M J, Michalska A E, O’Brien C M, et al. Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei. Curr Biol, 2000, 10: 989–992, 10985386, 10.1016/S0960-9822(00)00648-5, 1:CAS:528:DC%2BD3cXmtVGiurg%3DPubMedCrossRefGoogle Scholar
  8. 8.
    Cowan C A, Atienza J, Melton D A, et al. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science, 2005, 309: 1369–1373, 16123299, 10.1126/science.1116447, 1:CAS:528:DC%2BD2MXovVOjtLw%3DPubMedCrossRefGoogle Scholar
  9. 9.
    Guan K, Nayernia K, Maier L S, et al. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature, 2006, 440: 1199–1203, 16565704, 10.1038/nature04697, 1:CAS:528:DC%2BD28XjvVGltbw%3DPubMedCrossRefGoogle Scholar
  10. 10.
    Conrad S, Renninger M, Hennenlotter J, et al. Generation of pluripotent stem cells from adult human testis. Nature, 2008, 456: 344–349, 18849962, 10.1038/nature07404, 1:CAS:528:DC%2BD1cXhsVSjsLjIPubMedCrossRefGoogle Scholar
  11. 11.
    Kanatsu-Shinohara M, Inoue K, Lee J, et al. Generation of pluripotent stem cells from neonatal mouse testis. Cell, 2004, 119: 1001–1012, 15620358, 10.1016/j.cell.2004.11.011, 1:CAS:528:DC%2BD2MXltlSiuw%3D%3DPubMedCrossRefGoogle Scholar
  12. 12.
    Hochedlinger K, Jaenisch R. Nuclear reprogramming and pluripotency. Nature, 2006, 441: 1061–1067, 16810240, 10.1038/nature04955, 1:CAS:528:DC%2BD28Xmtlahsrg%3DPubMedCrossRefGoogle Scholar
  13. 13.
    Shamblott M J, Axelman J, Wang S, et al. Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci USA, 1998, 95: 13726–13731, 9811868, 10.1073/pnas.95.23.13726, 1:CAS:528:DyaK1cXnsVGhur0%3DPubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Matsui Y, Toksoz D, Nishikawa S, et al. Effect of Steel factor and leukaemia inhibitory factor on murine primordial germ cells in culture. Nature, 1991, 353: 750–752, 1719421, 10.1038/353750a0, 1:STN:280:DyaK38%2FkvFOjsw%3D%3DPubMedCrossRefGoogle Scholar
  15. 15.
    Brons I G, Smithers L E, Trotter M W, et al. Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature, 2007, 448: 191–195, 17597762, 10.1038/nature05950, 1:CAS:528:DC%2BD2sXnsFeisbw%3DPubMedCrossRefGoogle Scholar
  16. 16.
    Tesar P J, Chenoweth J G, Brook F A, et al. New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature, 2007, 448: 196–199, 17597760, 10.1038/nature05972, 1:CAS:528:DC%2BD2sXnsFeisbk%3DPubMedCrossRefGoogle Scholar
  17. 17.
    Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006, 126: 663–676, 16904174, 10.1016/j.cell.2006.07.024, 1:CAS:528:DC%2BD28Xpt1aktbs%3DPubMedCrossRefGoogle Scholar
  18. 18.
    Tokuzawa Y, Kaiho E, Maruyama M, et al. Fbx15 is a novel target of Oct3/4 but is dispensable for embryonic stem cell self-renewal and mouse development. Mol Cell Biol, 2003, 23: 2699–2708, 12665572, 10.1128/MCB.23.8.2699-2708.2003, 1:CAS:528:DC%2BD3sXktV2lsbg%3DPubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Chambers I, Colby D, Robertson M, et al. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell, 2003, 113: 643–655, 12787505, 10.1016/S0092-8674(03)00392-1, 1:CAS:528:DC%2BD3sXksFehur8%3DPubMedCrossRefGoogle Scholar
  20. 20.
    Nichols J, Zevnik B, Anastassiadis K, et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell, 1998, 95: 379–391, 9814708, 10.1016/S0092-8674(00)81769-9, 1:CAS:528:DyaK1cXntlCqt74%3DPubMedCrossRefGoogle Scholar
  21. 21.
    Mitsui K, Tokuzawa Y, Itoh H, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell, 2003, 113: 631–642, 12787504, 10.1016/S0092-8674(03)00393-3, 1:CAS:528:DC%2BD3sXksFehur4%3DPubMedCrossRefGoogle Scholar
  22. 22.
    Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature, 2007, 448: 313–317, 17554338, 10.1038/nature05934, 1:CAS:528:DC%2BD2sXnvVeqsL0%3DPubMedCrossRefGoogle Scholar
  23. 23.
    Wernig M, Meissner A, Foreman R, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature, 2007, 448: 318–324, 17554336, 10.1038/nature05944, 1:CAS:528:DC%2BD2sXnvVeqsLg%3DPubMedCrossRefGoogle Scholar
  24. 24.
    Maherali N, Sridharan R, Xie W, et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell, 2007, 1: 55–70, 18371336, 10.1016/j.stem.2007.05.014, 1:CAS:528:DC%2BD2sXptV2rs74%3DPubMedCrossRefGoogle Scholar
  25. 25.
    Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 2007, 131: 861–872, 18035408, 10.1016/j.cell.2007.11.019, 1:CAS:528:DC%2BD2sXhsVCntbbKPubMedCrossRefGoogle Scholar
  26. 26.
    Yu J, Vodyanik M A, muga-OttoK S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science, 2007, 318: 1917–1920, 18029452, 10.1126/science.1151526, 1:CAS:528:DC%2BD2sXhsVGjsLbNPubMedCrossRefGoogle Scholar
  27. 27.
    Park I H, Zhao R, West J A, et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 2008, 451: 141–146, 18157115, 10.1038/nature06534, 1:CAS:528:DC%2BD1cXksVGhtQ%3D%3DPubMedCrossRefGoogle Scholar
  28. 28.
    Lowry W E, Richter L, Yachechko R, et al. Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci USA, 2008, 105: 2883–2888, 18287077, 10.1073/pnas.0711983105, 1:CAS:528:DC%2BD1cXjtVSisr0%3DPubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Park I H, Arora N, Huo H, et al. Disease-specific induced pluripotent stem cells. Cell, 2008, 134: 877–886, 18691744, 10.1016/j.cell.2008.07.041, 1:CAS:528:DC%2BD1cXhtFCqs7bKPubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Dimos J T, Rodolfa K T, Niakan K K, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science, 2008, 321: 1218–1221, 18669821, 10.1126/science.1158799, 1:CAS:528:DC%2BD1cXhtVGgt7zLPubMedCrossRefGoogle Scholar
  31. 31.
    Huangfu D, Osafune K, Maehr R, et al. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol, 2008, 26: 1269–1275, 18849973, 10.1038/nbt.1502, 1:CAS:528:DC%2BD1cXhtlCktrvEPubMedCrossRefGoogle Scholar
  32. 32.
    Aasen T, Raya A, Barrero M J, et al. Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nat Biotechnol, 2008, 26: 1276–1284, 18931654, 10.1038/nbt.1503, 1:CAS:528:DC%2BD1cXhtlCktrvOPubMedCrossRefGoogle Scholar
  33. 33.
    Maherali N, Ahfeldt T, Rigamonti A, et al. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell, 2008, 3: 340–345, 18786420, 10.1016/j.stem.2008.08.003, 1:CAS:528:DC%2BD1cXhtF2jtr%2FJPubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Hockemeyer D, Soldner F, Cook E G, et al. A drug-inducible system for direct reprogramming of human somatic cells to pluripotency. Cell Stem Cell, 2008, 3: 346–353, 18786421, 10.1016/j.stem.2008.08.014, 1:CAS:528:DC%2BD1cXhtF2jtr%2FKPubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Liu H, Zhu F, Yong J, et al. Generation of induced pluripotent stem cells from adult rhesus monkey fibroblasts. Cell Stem Cell, 2008, 3: 587–590, 19041774, 10.1016/j.stem.2008.10.014, 1:CAS:528:DC%2BD1cXhsFCqsLjNPubMedCrossRefGoogle Scholar
  36. 36.
    Li W, Wei W, Zhu S, et al. Generation of Rat and Human Induced Pluripotent Stem Cells by Combining Genetic Reprogramming and Chemical Inhibitors. Cell Stem Cell, 2009, 4: 16–19, 19097958, 10.1016/j.stem.2008.11.014PubMedCrossRefGoogle Scholar
  37. 37.
    Liao J, Cui C, Chen S, et al. Generation of Induced Pluripotent Stem Cell Lines from Adult Rat Cells. Cell Stem Cell, 2009, 4: 11–15, 19097959, 10.1016/j.stem.2008.11.013, 1:CAS:528:DC%2BD1MXhtVSksrk%3DPubMedCrossRefGoogle Scholar
  38. 38.
    Esteban M A, Xu J, Yang J, et al. Generation of induced pluripotent stem cell lines from tibetan miniature pig. J Biol Chem, 2009, 284: 17634–17640, 19376775, 10.1074/jbc.M109.008938, 1:CAS:528:DC%2BD1MXnsVWks7g%3DPubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Wu Z, Chen J, Ren J, et al. Generation of pig-induced pluripotent stem cells with a drug-inducible system. J Mol Cell Biol, 2009, doi:10.10931jmcb/mjp003Google Scholar
  40. 40.
    Meissner A, Wernig M, Jaenisch R. Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol, 2007, 25: 1177–1181, 17724450, 10.1038/nbt1335, 1:CAS:528:DC%2BD2sXhtFagt7rLPubMedCrossRefGoogle Scholar
  41. 41.
    Qin D, Li W, Zhang J, et al. Direct generation of ES-like cells from unmodified mouse embryonic fibroblasts by Oct4/Sox2/Myc/Klf4. Cell Res, 2007, 17: 959–962, 17971807, 10.1038/cr.2007.92, 1:CAS:528:DC%2BD2sXhtlWjsbvJPubMedCrossRefGoogle Scholar
  42. 42.
    Zhao Y, Yin X, Qin H, et al. Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell, 2008, 3: 475–479, 18983962, 10.1016/j.stem.2008.10.002, 1:CAS:528:DC%2BD1cXhsVaqs77KPubMedCrossRefGoogle Scholar
  43. 43.
    Meyer N, Penn L Z. Reflecting on 25 years with MYC. Nat Rev Cancer, 2008, 8: 976–990, 19029958, 10.1038/nrc2231, 1:CAS:528:DC%2BD1cXhsVWhu7rJPubMedCrossRefGoogle Scholar
  44. 44.
    Rowland B D, Peeper D S. KLF4, p21 and context-dependent opposing forces in cancer. Nat Rev Cancer, 2006, 6: 11–23, 16372018, 10.1038/nrc1780, 1:CAS:528:DC%2BD28Xht1GgsQ%3D%3DPubMedCrossRefGoogle Scholar
  45. 45.
    Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol, 2008, 26: 101–106, 18059259, 10.1038/nbt1374, 1:CAS:528:DC%2BD1cXisFGmuw%3D%3DPubMedCrossRefGoogle Scholar
  46. 46.
    Wernig M, Meissner A, Cassady J P, et al. c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell, 2008, 2: 10–12, 18371415, 10.1016/j.stem.2007.12.001, 1:CAS:528:DC%2BD1cXhtFOltrc%3DPubMedCrossRefGoogle Scholar
  47. 47.
    Hanna, J, M Wernig, S Markoulaki, et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science, 2007, 318: 1920–1923, 18063756, 10.1126/science.1152092, 1:CAS:528:DC%2BD2sXhsVGjsLbPPubMedCrossRefGoogle Scholar
  48. 48.
    Stadtfeld M, Maherali N, Breault D T, et al. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell, 2008, 2: 230–240, 18371448, 10.1016/j.stem.2008.02.001, 1:CAS:528:DC%2BD1cXjslegtrw%3DPubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Brambrink T, Foreman R, Welstead G G, et al. Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell, 2008, 2: 151–159, 18371436, 10.1016/j.stem.2008.01.004, 1:CAS:528:DC%2BD1cXitlygtbw%3DPubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Sommer C A, Stadtfeld M, Murphy G J, et al. iPS cell generation using a single lentiviral stem cell cassette. Stem Cells, 2008, 27: 543–549, 10.1634/stemcells.2008-1075CrossRefGoogle Scholar
  51. 51.
    Carey B W, Markoulaki S, Hanna J, et al. Reprogramming of murine and human somatic cells using a single polycistronic vector. Proc Natl Acad Sci U S A, 2009, 106: 157–162, 19109433, 10.1073/pnas.0811426106, 1:CAS:528:DC%2BD1MXltF2msg%3D%3DPubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Aoi T, Yae K, Nakagawa M, et al. Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science, 2008, 321: 699–702, 18276851, 10.1126/science.1154884, 1:CAS:528:DC%2BD1cXptVKnu78%3DPubMedCrossRefGoogle Scholar
  53. 53.
    Stadtfeld M, Nagaya M, Utikal J, et al. Induced pluripotent stem cells generated without viral integration. Science, 2008, 322: 945–949, 18818365, 10.1126/science.1162494, 1:CAS:528:DC%2BD1cXhtlaltLzNPubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Kaji K, Norrby K, Paca A, et al. Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature, 2009, 458: 771–775, 19252477, 10.1038/nature07864, 1:CAS:528:DC%2BD1MXisVOrtbk%3DPubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Okita K, Nakagawa M, Hyenjong H, et al. Generation of mouse induced pluripotent stem cells without viral vectors. Science, 2008, 322: 949–953, 18845712, 10.1126/science.1164270, 1:CAS:528:DC%2BD1cXhtlaltLzOPubMedCrossRefGoogle Scholar
  56. 56.
    Woltjen K, Michael I P, Mohseni P, et al. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature, 2009, 458: 766–770, 19252478, 10.1038/nature07863, 1:CAS:528:DC%2BD1MXisVOrtr0%3DPubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Zhou H, Wu S, Joo J Y, et al. Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell, 2009, 4: 381–384, 19398399, 10.1016/j.stem.2009.04.005, 1:CAS:528:DC%2BD1MXlvVGjtLw%3DPubMedCrossRefGoogle Scholar
  58. 58.
    Hanna J, Markoulaki S, Schorderet P, et al. Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell, 2008, 133: 250–264, 18423197, 10.1016/j.cell.2008.03.028, 1:CAS:528:DC%2BD1cXltlWnu78%3DPubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Mikkelsen T S, Hanna J, Zhang X, et al. Dissecting direct reprogramming through integrative genomic analysis. Nature, 2008, 454: 49–55, 18509334, 10.1038/nature07056, 1:CAS:528:DC%2BD1cXotVertb4%3DPubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Marson A, Foreman R, Chevalier B, et al. Wnt signaling promotes reprogramming of somatic cells to pluripotency. Cell Stem Cell, 2008, 3: 132–135, 18682236, 10.1016/j.stem.2008.06.019, 1:CAS:528:DC%2BD1cXhtVegtr7NPubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Huangfu D, Maehr R, Guo W, et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol, 2008, 26: 795–797, 18568017, 10.1038/nbt1418, 1:CAS:528:DC%2BD1cXot1entL0%3DPubMedCrossRefGoogle Scholar
  62. 62.
    Feng B, Jiang J, Kraus P, et al. Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat Cell Biol, 2009, 11: 197–203, 19136965, 10.1038/ncb1827, 1:CAS:528:DC%2BD1MXht1Oqt78%3DPubMedCrossRefGoogle Scholar
  63. 63.
    Kim J B, Zaehres H, Wu G, et al. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature, 2008, 454: 646–650, 18594515, 10.1038/nature07061, 1:CAS:528:DC%2BD1cXptFOksrY%3DPubMedCrossRefGoogle Scholar
  64. 64.
    Eminli S, Utikal J, Arnold K, et al. Reprogramming of neural progenitor cells into induced pluripotent stem cells in the absence of exogenous Sox2 expression. Stem Cells, 2008, 26: 2467–2474, 18635867, 10.1634/stemcells.2008-0317, 1:CAS:528:DC%2BD1cXhtlyku7rMPubMedCrossRefGoogle Scholar
  65. 65.
    Shi Y, Do J T, Desponts C, et al. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell, 2008, 2: 525–528, 18522845, 10.1016/j.stem.2008.05.011, 1:CAS:528:DC%2BD1cXntFalsLo%3DPubMedCrossRefGoogle Scholar
  66. 66.
    Shi Y, Desponts C, Do J T, et al. Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell, 2008, 3: 568–574, 18983970, 10.1016/j.stem.2008.10.004, 1:CAS:528:DC%2BD1cXhsVaqs7%2FJPubMedCrossRefGoogle Scholar
  67. 67.
    Silva J, Barrandon O, Nichols J, et al. Promotion of reprogramming to ground state pluripotency by signal inhibition. PLoS Biol, 2008, 6: e253, 18942890, 10.1371/journal.pbio.0060253PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Kim J B, Sebastiano V, Wu G, et al. Oct4-induced pluripotency in adult neural stem cells. Cell, 2009, 136: 411–419, 19203577, 10.1016/j.cell.2009.01.023, 1:CAS:528:DC%2BD1MXltFSnsr4%3DPubMedCrossRefGoogle Scholar
  69. 69.
    Ebert A D, Yu J, Rose F F Jr, et al. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature, 2009, 457: 277–280, 19098894, 10.1038/nature07677, 1:CAS:528:DC%2BD1MXlvFWnsw%3D%3DPubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Loh Y H, Agarwal S, Park I H, et al. Generation of induced pluripotent stem cells from human blood. Blood, 2009, 113: 5476–5479, 19299331, 10.1182/blood-2009-02-204800, 1:CAS:528:DC%2BD1MXntVertbs%3DPubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Yu J, Hu K, Smuga-Otto K, et al. Human induced pluripotent stem cells free of vector and transgene sequences. Science, 2009, 324: 797–801, 19325077, 10.1126/science.1172482, 1:CAS:528:DC%2BD1MXlsVeksrk%3DPubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Kim D, Kim C H, Moon J I, et al. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell, 2009, 4: 472–476, 19481515, 10.1016/j.stem.2009.05.005, 1:CAS:528:DC%2BD1MXnt1Ggt7o%3DPubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Lin S L, Chang D C, Chang-Lin S, et al. Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state. RNA, 2008, 14: 2115–2124, 18755840, 10.1261/rna.1162708, 1:CAS:528:DC%2BD1cXht1ektLfKPubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Soldner F, Hockemeyer D, Beard C, et al. Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 2009, 136: 964–977, 19269371, 10.1016/j.cell.2009.02.013, 1:CAS:528:DC%2BD1MXltFSnsb0%3DPubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Boyer L A, Lee T I, Cole M F, et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell, 2005, 122: 947–956, 16153702, 10.1016/j.cell.2005.08.020, 1:CAS:528:DC%2BD2MXhtVOrurbJPubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Loh Y H, Wu Q, Chew J L, et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet, 2006, 38: 431–440, 16518401, 10.1038/ng1760, 1:CAS:528:DC%2BD28XivFSht7c%3DPubMedCrossRefGoogle Scholar
  77. 77.
    Jiang J, Chan Y S, Loh Y H, et al. A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol, 2008, 10: 353–360, 18264089, 10.1038/ncb1698PubMedCrossRefGoogle Scholar
  78. 78.
    Kim J, Chu J, Shen X, et al. An extended transcriptional network for pluripotency of embryonic stem cells. Cell, 2008, 132: 1049–1061, 18358816, 10.1016/j.cell.2008.02.039, 1:CAS:528:DC%2BD1cXkt1WqsLg%3DPubMedCrossRefGoogle Scholar
  79. 79.
    Chen X, Xu H, Yuan P, et al. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell, 2008, 133: 1106–1117, 18555785, 10.1016/j.cell.2008.04.043, 1:CAS:528:DC%2BD1cXnsF2gurw%3DPubMedCrossRefGoogle Scholar
  80. 80.
    Marson A, Levine S S, Cole M F, et al. Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells. Cell, 2008, 134: 521–533, 18692474, 10.1016/j.cell.2008.07.020, 1:CAS:528:DC%2BD1cXhtVSis7zOPubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Sridharan R, Tchieu J, Mason M J, et al. Role of the murine reprogramming factors in the induction of pluripotency. Cell, 2009, 136: 364–377, 19167336, 10.1016/j.cell.2009.01.001, 1:CAS:528:DC%2BD1MXhs1Kiu7s%3DPubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Viswanathan S R, Daley G Q, Gregory R I. Selective Blockade of MicroRNA Processing by Lin-28. Science, 2008, 320: 97–100, 18292307, 10.1126/science.1154040, 1:CAS:528:DC%2BD1cXktVKht7k%3DPubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Judson R L, Babiarz J E, Venere M, et al. Embryonic stem cell-specific microRNAs promote induced pluripotency. Nat Biotechnol, 2009, 27: 459–461, 19363475, 10.1038/nbt.1535, 1:CAS:528:DC%2BD1MXksVekt78%3DPubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Marion R M, Strati K, Li H, et al. Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell, 2009, 4: 141–154, 19200803, 10.1016/j.stem.2008.12.010, 1:CAS:528:DC%2BD1MXitFSjtLk%3DPubMedCrossRefGoogle Scholar
  85. 85.
    Xu D, Alipio Z, Fink L M, et al. Phenotypic correction of murine hemophilia A using an iPS cell-based therapy. Proc Natl Acad Sci USA, 2009, 106: 808–813, 19139414, 10.1073/pnas.0812090106, 1:CAS:528:DC%2BD1MXht12isb0%3DPubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Raya A, Rodriguez-Piza I, Guenechea G, et al. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature, 2009, doi: 10.1038/nature08129Google Scholar
  87. 87.
    Lu S J, Feng Q, Park J S, et al. Biologic properties and enucleation of red blood cells from human embryonic stem cells. Blood, 2008, 112: 4475–4484, 18713948, 10.1182/blood-2008-05-157198, 1:CAS:528:DC%2BD1cXhsVCltb3IPubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Wernig M, Zhao J P, Pruszak J, et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci USA, 2008, 105: 5856–5861, 18391196, 10.1073/pnas.0801677105, 1:CAS:528:DC%2BD1cXltVyis70%3DPubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Narazaki G, Uosaki H, Teranishi M, et al. Directed and systematic differentiation of cardiovascular cells from mouse induced pluripotent stem cells. Circulation, 2008, 118: 498–506, 18625891, 10.1161/CIRCULATIONAHA.108.769562PubMedCrossRefGoogle Scholar
  90. 90.
    Zhang J, Wilson G F, Soerens A G, et al. Functional Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells. Circ Res, 2009, 104: e30–41, 19213953, 10.1161/CIRCRESAHA.108.192237, 1:CAS:528:DC%2BD1MXhvFejtb4%3DPubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Park T S, Galic Z, Conway A E, et al. Derivation of primordial germ cells from human embryonic and induced pluripotent stem cells is significantly improved by co-culture with human fetal gonadal cell. Stem Cells, 2009, 27: 783–795, 19350678, 10.1002/stem.13, 1:CAS:528:DC%2BD1MXmt1WnsLs%3DPubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Choi K, Yu J, Smuga-Otto K, et al. Hematopoietic and enodthelial differentiation of human induced pluripotent stem cells. Stem Cells, 2009, 27: 559–567, 19259936, 1:CAS:528:DC%2BD1MXkvVKgur4%3DPubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Couzin J. Biotechnology. Celebration and concern over U.S. trial of embryonic stem cells. Science, 2009, 323: 568, 19179496, 10.1126/science.323.5914.568, 1:CAS:528:DC%2BD1MXhsVKmtLc%3DPubMedCrossRefGoogle Scholar

Copyright information

© Science in China Press and Springer-Verlag GmbH 2009

Authors and Affiliations

  1. 1.Key Laboratory of Bioactive Materials of Ministry of Education, College of Life SciencesNankai UniversityTianjinChina

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