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Generation of Induced Pluripotent Stem Cells from Somatic Cells

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Nuclear Reprogramming and Stem Cells

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Pluripotent stem cells have been thought to be useful sources for regenerative medicine. Although embryonic stem (ES) cells have abilities to differentiate into several kinds of somatic cells and grow infinitely in vitro, there are several problems with using ES cells for clinical application such as ethical issues and rejection after transplantation. To overcome these problems, pluripotent stem cells were generated from somatic cells by introduction of defined factors. These have been termed induced pluripotent stem (iPS) cells. iPS cells have raised hopes for a new era of regenerative medicine because they can avoid the ethical problems and innate immune rejection associated with ES cells. In this chapter, I look back at the story of generation of iPS cells and discuss recent understanding of iPS cells with our latest data.

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References

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Barrett J, Birrer MJ, Kato GJ, Dosaka-Akita H, Dang CV (1992) Activation domains of L-Myc and c-Myc determine their transforming potencies in rat embryo cells. Mol Cell Biol 12:3130–3137

    PubMed  CAS  Google Scholar 

  • Birrer MJ, Segal S, DeGreve JS, Kaye F, Sausville EA, Minna JD (1988) L-myc cooperates with ras to transform primary rat embryo fibroblasts. Mol Cell Biol 8:2668–2673

    PubMed  CAS  Google Scholar 

  • Blackwell TK, Huang J, Ma A, Kretzner L, Alt FW, Eisenman RN, Weintraub H (1993) Binding of myc proteins to canonical and noncanonical DNA sequences. Mol Cell Biol 13:5216–5224

    PubMed  CAS  Google Scholar 

  • Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG et al (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947–956

    Article  PubMed  CAS  Google Scholar 

  • Carey BW, Markoulaki S, Hanna J, Saha K, Gao Q, Mitalipova M, Jaenisch R (2008) Reprogramming of murine and human somatic cells using a single polycistronic vector. Proc Natl Acad Sci U S A 106(1):157–162

    Article  PubMed  Google Scholar 

  • Cole MD (1986) The myc oncogene: its role in transformation and differentiation. Annu Rev Genet 20:361–384

    Article  PubMed  CAS  Google Scholar 

  • Cole MD, Cowling VH (2008) Transcription-independent functions of MYC: regulation of translation and DNA replication. Nat Rev Mol Cell Biol 9:810–815

    Article  PubMed  CAS  Google Scholar 

  • Davis RL, Weintraub H, Lassar AB (1987) Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51:987–1000

    Article  PubMed  CAS  Google Scholar 

  • 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 85:348–362

    Article  CAS  Google Scholar 

  • Gonzalez F, Barragan Monasterio M, Tiscornia G, Montserrat Pulido N, Vassena R, Batlle Morera L, Rodriguez Piza I, Belmonte JC (2009) Generation of mouse-induced pluripotent stem cells by transient expression of a single nonviral polycistronic vector. Proc Natl Acad Sci U S A 106(22):8918–8922

    Article  PubMed  CAS  Google Scholar 

  • Gurdon JB, Uehlinger V (1966) “Fertile” intestine nuclei. Nature 210:1240–1241

    Article  PubMed  CAS  Google Scholar 

  • Hatton KS, Mahon K, Chin L, Chiu FC, Lee HW, Peng D, Morgenbesser SD, Horner J, DePinho RA (1996) Expression and activity of L-Myc in normal mouse development. Mol Cell Biol 16:1794–1804

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Hotta A, Cheung AY, Farra N, Garcha K, Chang WY, Pasceri P, Stanford WL, Ellis J (2009a) EOS lentiviral vector selection system for human induced pluripotent stem cells. Nat Protoc 4:1828–1844

    Article  PubMed  CAS  Google Scholar 

  • Hotta A, Cheung AY, Farra N, Vijayaragavan K, Seguin CA, Draper JS, Pasceri P, Maksakova IA, Mager DL, Rossant J et al (2009b) Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nat Methods 6:370–376

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K (2009) Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 458(7239):771–775

    Article  PubMed  CAS  Google Scholar 

  • Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R et al (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476

    Article  PubMed  CAS  Google Scholar 

  • 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. Proc Natl Acad Sci U S A 106(22):8912–8917

    Article  PubMed  Google Scholar 

  • 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 remodelling and widespread tissue contribution. Cell Stem Cell 1:55–70

    Article  PubMed  CAS  Google Scholar 

  • Malynn BA, de Alboran IM, O’Hagan RC, Bronson R, Davidson L, DePinho RA, Alt FW (2000) N-myc can functionally replace c-myc in murine development, cellular growth, and differentiation. Genes Dev 14:1390–1399

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Miura K, Okada Y, Aoi T, Okada A, Takahashi K, Okita K, Nakagawa M, Koyanagi M, Tanabe K, Ohnuki M et al (2009) Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol 8:743–745

    Article  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa M, Takizawa N, Narita M, Ichisaka T, Yamanaka S (2010) Promotion of direct reprogramming by transformation-deficient Myc. Proc Natl Acad Sci U S A 107:14152–14157

    Article  PubMed  CAS  Google Scholar 

  • Okita K, Ichisaka T, Yamanaka S (2007) Generation of germ-line competent induced pluripotent stem cells. Nature 448:313–317

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Oster SK, Mao DY, Kennedy J, Penn LZ (2003) Functional analysis of the N-terminal domain of the Myc oncoprotein. Oncogene 22:1998–2010

    Article  PubMed  CAS  Google Scholar 

  • Schwab M, Varmus HE, Bishop JM (1985) Human N-myc gene contributes to neoplastic transformation of mammalian cells in culture. Nature 316:160–162

    Article  PubMed  CAS  Google Scholar 

  • Shao L, Feng W, Sun Y, Bai H, Liu J, Currie C, Kim J, Gama R, Wang Z, Qian Z et al (2009) Generation of iPS cells using defined factors linked via the self-cleaving 2A sequences in a single open reading frame. Cell Res 19(3):296–306

    Article  PubMed  CAS  Google Scholar 

  • Smith KN, Singh AM, Dalton S (2010) Myc represses primitive endoderm differentiation in pluripotent stem cells. Cell Stem Cell 7:343–354

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Sommer CA, Stadtfeld M, Murphy GJ, Hochedlinger K, Kotton DN, Mostoslavsky G (2009) iPS cell generation using a single lentiviral stem cell cassette. Stem Cells 27(3):543–549

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K (2008) Induced pluripotent stem cells generated without viral integration. Science 322:945–949

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Taylor SM, Jones PA (1979) Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell 17:771–779

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Wernig M, Meissner A, Cassady JP, Jaenisch R (2008) c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell 2:10–12

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Yancopoulos GD, Nisen PD, Tesfaye A, Kohl NE, Goldfarb MP, Alt FW (1985) N-myc can cooperate with ras to transform normal cells in culture. Proc Natl Acad Sci U S A 82:5455–5459

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II, Thomson JA (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324:797–801

    Article  PubMed  CAS  Google Scholar 

  • Yusa K, Rad R, Takeda J, Bradley A (2009) Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon. Nat Methods 6:363–369

    Article  PubMed  CAS  Google Scholar 

  • Zhou W, Freed CR (2009) Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells. Stem Cells 27:2667–2674

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan

    Masato Nakagawa

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  1. Masato Nakagawa
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Correspondence to Masato Nakagawa .

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Editors and Affiliations

  1. Leeds Institute of Genetics,, Health & Therapeutics, University of Leeds, Leeds, LS2 9JT, United Kingdom

    Justin Ainscough

  2. Inst. Frontier Medical Sciences, Kyoto University, Kawahara-cho 53, Kyoto, 606-8507, Japan

    Shinya Yamanaka

  3. Inst. Frontier Medical Sciences, Kyoto University, Kawahara-cho 53, Kyoto, 606-8507, Japan

    Takashi Tada

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Nakagawa, M. (2011). Generation of Induced Pluripotent Stem Cells from Somatic Cells. In: Ainscough, J., Yamanaka, S., Tada, T. (eds) Nuclear Reprogramming and Stem Cells. Stem Cell Biology and Regenerative Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-225-0_7

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