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In Vivo Cell Reprogramming to Pluripotency

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In Vivo Reprogramming in Regenerative Medicine

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

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Abstract

The stem cell field witnessed a genuine breakthrough when a combination of solely four transcription factors (Oct3/4, Sox2, Klf4 and c-Myc, OSKM) proved enough to revert, in vitro, the differentiated status of a variety of cell types back to pluripotency, giving rise to so-called induced pluripotent stem (iPS) cells. Ten years after this revolutionary discovery, attempts to induce pluripotency have not been limited to the culture dish. Some studies have interrogated the downstream effects of the overexpression of OSKM reprogramming factors in the living organism. In this Chapter, we dissect the proof-of-principle studies that demonstrated that cellular reprogramming to pluripotency can be induced in vivo, in spite of unfavorable pro-differentiation signals present within the tissues. The links of in vivo reprogramming to pluripotency with tumorigenesis and teratoma formation, and the cross-talk with cellular senesce and tissue injury are also discussed.

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References

  1. Brunt KR, Weisel RD, Li RK. Stem cells and regenerative medicine - future perspectives. Can J Physiol Pharmacol. 2012;90(3):327–35. doi:10.1139/y2012-007.

    Article  CAS  PubMed  Google Scholar 

  2. Ilic D, Polak JM. Stem cells in regenerative medicine: introduction. Br Med Bull. 2011;98:117–26. doi:10.1093/bmb/ldr012.

    Article  PubMed  Google Scholar 

  3. Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A. 1981;78(12):7634–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292(5819):154–6.

    Article  CAS  PubMed  Google Scholar 

  5. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145–7.

    Article  CAS  PubMed  Google Scholar 

  6. Nichols J, Evans EP, Smith AG. Establishment of germ-line-competent embryonic stem (ES) cells using differentiation inhibiting activity. Development. 1990;110(4):1341–8.

    CAS  PubMed  Google Scholar 

  7. Evans MD, Kelley J. US attitudes toward human embryonic stem cell research. Nat Biotechnol. 2011;29(6):484–8. doi:10.1038/nbt.1891.

    Article  CAS  PubMed  Google Scholar 

  8. Wilmut I. Consternation and confusion following EU patent judgment. Cell Stem Cell. 2011;9(6):498–9. doi:10.1016/j.stem.2011.11.002.

    Article  CAS  PubMed  Google Scholar 

  9. Gurdon JB. The developmental capacity of nuclei taken from differentiating endoderm cells of Xenopus laevis. J Embryol Exp Morphol. 1960;8:505–26.

    CAS  PubMed  Google Scholar 

  10. Gurdon JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol. 1962;10:622–40.

    CAS  PubMed  Google Scholar 

  11. Gurdon JB, Laskey RA, Reeves OR. The developmental capacity of nuclei transplanted from keratinized skin cells of adult frogs. J Embryol Exp Morphol. 1975;34(1):93–112.

    CAS  PubMed  Google Scholar 

  12. Davis RL, Weintraub H, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987;51(6):987–1000. doi:10.1016/0092-8674(87)90585-x.

    Article  CAS  PubMed  Google Scholar 

  13. Weintraub H, Tapscott SJ, Davis RL, Thayer MJ, Adam MA, Lassar AB, Miller AD. Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci U S A. 1989;86(14):5434–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Briggs R, King TJ. Transplantation of living nuclei from blastula cells into enucleated frogs’ eggs. Proc Natl Acad Sci U S A. 1952;38(5):455–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Viable offspring derived from fetal and adult mammalian cells. Nature. 1997;385(6619):810–3. doi:10.1038/385810a0.

    Article  CAS  PubMed  Google Scholar 

  16. Miller RA, Ruddle FH. Pluripotent teratocarcinoma-thymus somatic cell hybrids. Cell. 1976;9(1):45–55. doi:10.1016/0092-8674(76)90051-9.

    Article  CAS  PubMed  Google Scholar 

  17. Egli D, Chen AE, Saphier G, Ichida J, Fitzgerald C, Go KJ, Acevedo N, Patel J, Baetscher M, Kearns WG, Goland R, Leibel RL, Melton DA, Eggan K. Reprogramming within hours following nuclear transfer into mouse but not human zygotes. Nat Commun. 2011;2:488. doi:10.1038/ncomms1503.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Noggle S, Fung HL, Gore A, Martinez H, Satriani KC, Prosser R, Oum K, Paull D, Druckenmiller S, Freeby M, Greenberg E, Zhang K, Goland R, Sauer MV, Leibel RL, Egli D. Human oocytes reprogram somatic cells to a pluripotent state. Nature. 2011;478(7367):70–5. doi:10.1038/nature10397.

    Article  CAS  PubMed  Google Scholar 

  19. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76. doi:10.1016/j.cell.2006.07.024.

    Article  CAS  PubMed  Google Scholar 

  20. Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007;448(7151):313–7. doi:10.1038/nature05934.

    Article  CAS  PubMed  Google Scholar 

  21. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72. doi:10.1016/j.cell.2007.11.019.

    Article  CAS  PubMed  Google Scholar 

  22. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–20. doi:10.1126/science.1151526.

    Article  CAS  PubMed  Google Scholar 

  23. Polo Jose M, Anderssen E, Walsh Ryan M, Schwarz Benjamin A, Nefzger Christian M, Lim Sue M, Borkent M, Apostolou E, Alaei S, Cloutier J, Bar-Nur O, Cheloufi S, Stadtfeld M, Figueroa Maria E, Robinton D, Natesan S, Melnick A, Zhu J, Ramaswamy S, Hochedlinger K. A molecular roadmap of reprogramming somatic cells into iPS cells. Cell. 2012;151(7):1617–32. doi:10.1016/j.cell.2012.11.039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Buganim Y, Faddah DA, Jaenisch R. Mechanisms and models of somatic cell reprogramming. Nat Rev Genet. 2013;14(6):427–39. doi:10.1038/nrg3473.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, Chiba T, Yamanaka S. Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science. 2008;321(5889):699–702. doi:10.1126/science.1154884.

    Article  CAS  PubMed  Google Scholar 

  26. Loh YH, Agarwal S, Park IH, Urbach A, Huo H, Heffner GC, Kim K, Miller JD, Ng K, Daley GQ. Generation of induced pluripotent stem cells from human blood. Blood. 2009;113(22):5476–9. doi:10.1182/blood-2009-02-204800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ruiz S, Brennand K, Panopoulos AD, Herrerias A, Gage FH, Izpisua-Belmonte JC. High-efficient generation of induced pluripotent stem cells from human astrocytes. PLoS One. 2010;5(12):e15526. doi:10.1371/journal.pone.0015526.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lowry WE, Richter L, Yachechko R, Pyle AD, Tchieu J, Sridharan R, Clark AT, Plath K. Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci U S A. 2008;105(8):2883–8. doi:10.1073/pnas.0711983105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Staerk J, Dawlaty MM, Gao Q, Maetzel D, Hanna J, Sommer CA, Mostoslavsky G, Jaenisch R. Reprogramming of human peripheral blood cells to induced pluripotent stem cells. Cell Stem Cell. 2010;7(1):20–4. doi:10.1016/j.stem.2010.06.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bellin M, Marchetto MC, Gage FH, Mummery CL. Induced pluripotent stem cells: the new patient? Nat Rev Mol Cell Biol. 2012;13(11):713–26. doi:10.1038/nrm3448.

    Article  PubMed  Google Scholar 

  31. de Lazaro I, Yilmazer A, Kostarelos K. Induced pluripotent stem (iPS) cells: a new source for cell-based therapeutics? J Control Release. 2014;185:37–44. doi:10.1016/j.jconrel.2014.04.011.

    Article  PubMed  Google Scholar 

  32. Silva J, Barrandon O, Nichols J, Kawaguchi J, Theunissen TW, Smith A. Promotion of reprogramming to ground state pluripotency by signal inhibition. PLoS Biol. 2008;6(10):2237–47. doi:10.1371/journal.pbio.0060253.

    Article  CAS  Google Scholar 

  33. Kawai H, Yamashita T, Ohta Y, Deguchi K, Nagotani S, Zhang X, Ikeda Y, Matsuura T, Abe K. Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain. J Cereb Blood Flow Metab. 2010;30(8):1487–93. doi:10.1038/jcbfm.2010.32.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ben-David U, Benvenisty N. The tumorigenicity of human embryonic and induced pluripotent stem cells. Nat Rev Cancer. 2011;11(4):268–77. doi:10.1038/nrc3034.

    Article  CAS  PubMed  Google Scholar 

  35. Hentze H, Soong PL, Wang ST, Phillips BW, Putti TC, Dunn NR. Teratoma formation by human embryonic stem cells: evaluation of essential parameters for future safety studies. Stem Cell Res. 2009;2(3):198–210. doi:10.1016/j.scr.2009.02.002.

    Article  PubMed  Google Scholar 

  36. Vivien C, Scerbo P, Girardot F, Le Blay K, Demeneix BA, Coen L. Non-viral expression of mouse Oct4, Sox2, and Klf4 transcription factors efficiently reprograms tadpole muscle fibers in vivo. J Biol Chem. 2012;287(10):7427–35. doi:10.1074/jbc.M111.324368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yilmazer A, de Lazaro I, Bussy C, Kostarelos K. In vivo cell reprogramming towards pluripotency by virus-free overexpression of defined factors. PLoS One. 2013;8(1):e54754. doi:10.1371/journal.pone.0054754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Yilmazer A, de Lazaro I, Bussy C, Kostarelos K. In vivo reprogramming of adult somatic cells to pluripotency by overexpression of Yamanaka factors. J Vis Exp. 2013;17(82):e50837.

    Google Scholar 

  39. Liu F, Song Y, Liu D. Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Ther. 1999;6(7):1258–66. doi:10.1038/sj.gt.3300947.

    Article  CAS  PubMed  Google Scholar 

  40. Andrianaivo F, Lecocq M, Wattiaux-De Coninck S, Wattiaux R, Jadot M. Hydrodynamics-based transfection of the liver: entrance into hepatocytes of DNA that causes expression takes place very early after injection. J Gene Med. 2004;6(8):877–83. doi:10.1002/jgm.574.

    Article  CAS  PubMed  Google Scholar 

  41. Sebestyen MG, Budker VG, Budker T, Subbotin VM, Zhang G, Monahan SD, Lewis DL, Wong SC, Hagstrom JE, Wolff JA. Mechanism of plasmid delivery by hydrodynamic tail vein injection. I. Hepatocyte uptake of various molecules. J Gene Med. 2006;8(7):852–73. doi:10.1002/jgm.921.

    Article  CAS  PubMed  Google Scholar 

  42. Banga A, Akinci E, Greder LV, Dutton JR, Slack JMW. In vivo reprogramming of Sox9+ cells in the liver to insulin-secreting ducts. Proc Natl Acad Sci U S A. 2012;109(38):15336–41. doi:10.1073/pnas.1201701109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. de Lazaro I, Bussy C, Yilmazer A, Jackson MS, Humphreys NE, Kostarelos K. Generation of induced pluripotent stem cells from virus-free in vivo reprogramming of BALB/c mouse liver cells. Biomaterials. 2014;35(29):8312–20. doi:10.1016/j.biomaterials.2014.05.086.

    Article  PubMed  Google Scholar 

  44. Sommer CA, Stadtfeld M, Murphy GJ, Hochedlinger K, Kotton DN, Mostoslavsky G. Induced pluripotent stem cell generation using a single lentiviral stem cell cassette. Stem Cells. 2009;27(3):543–9. doi:10.1634/stemcells.2008-1075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hamilton B, Feng Q, Ye M, Welstead GG. Generation of induced pluripotent stem cells by reprogramming mouse embryonic fibroblasts with a four transcription factor, doxycycline inducible lentiviral transduction system. J Vis Exp. 2009;33:1447. https://doi.org/10.3791/1447.

    Google Scholar 

  46. Sommer CA, Sommer AG, Longmire TA, Christodoulou C, Thomas DD, Gostissa M, Alt FW, Murphy GJ, Kotton DN, Mostoslavsky G. Excision of reprogramming transgenes improves the differentiation potential of iPS cells generated with a single excisable vector. Stem Cells. 2010;28(1):64–74. doi:10.1002/stem.255.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Tashiro K. Optimization of adenovirus vectors for transduction in embryonic stem cells and induced pluripotent stem cells. Yakugaku Zasshi. 2011;131(9):1333–8. doi:10.1248/yakushi.131.1333.

    Article  CAS  PubMed  Google Scholar 

  48. Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M. 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. 2009;85(8):348–62. doi:10.2183/pjab.85.348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science. 2008;322(5903):949–53. doi:10.1126/science.1164270.

    Article  CAS  PubMed  Google Scholar 

  50. Davis RP, Nemes C, Varga E, Freund C, Kosmidis G, Gkatzis K, de Jong D, Szuhai K, Dinnyes A, Mummery CL. Generation of induced pluripotent stem cells from human foetal fibroblasts using the sleeping beauty transposon gene delivery system. Differentiation. 2013;86(1-2):30–7. doi:10.1016/j.diff.2013.06.002.

    Article  CAS  PubMed  Google Scholar 

  51. Plews JR, Li J, Jones M, Moore HD, Mason C, Andrews PW, Na J. Activation of pluripotency genes in human fibroblast cells by a novel mRNA based approach. PLoS One. 2010;5(12):e14397. doi:10.1371/journal.pone.0014397.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell. 2011;8(4):376–88. doi:10.1016/j.stem.2011.03.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell. 2009;4(6):472–6. doi:10.1016/j.stem.2009.05.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. de Lazaro I, Yilmazer A, Nam Y, Qubisi S, Razak F, Cossu G, Kostarelos K. Non-viral induction of transient cell reprogramming in skeletal muscle to enhance tissue regeneration. bioRxiv. 2017. doi:10.1101/101188.

  55. Gao X, Wang X, Xiong W, Chen J. In vivo reprogramming reactive glia into iPSCs to produce new neurons in the cortex following traumatic brain injury. Sci Rep. 2016;6:22490. doi:10.1038/srep22490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Abad M, Mosteiro L, Pantoja C, Canamero M, Rayon T, Ors I, Grana O, Megias D, Dominguez O, Martinez D, Manzanares M, Ortega S, Serrano M. Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature. 2013;502:340–5. doi:10.1038/nature12586.

    Article  CAS  PubMed  Google Scholar 

  57. Ohnishi K, Semi K, Yamamoto T, Shimizu M, Tanaka A, Mitsunaga K, Okita K, Osafune K, Arioka Y, Maeda T, Soejima H, Moriwaki H, Yamanaka S, Woltjen K, Yamada Y. Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation. Cell. 2014;156(4):663–77. doi:10.1016/j.cell.2014.01.005.

    Article  CAS  PubMed  Google Scholar 

  58. Choi HW, Kim JS, Hong YJ, Song H, Seo HG, Do JT. In vivo reprogrammed pluripotent stem cells from teratomas share analogous properties with their in vitro counterparts. Sci Rep. 2015;5:13559. doi:10.1038/srep13559.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Mosteiro L, Pantoja C, Alcazar N, Marion RM, Chondronasiou D, Rovira M, Fernandez-Marcos PJ, Munoz-Martin M, Blanco-Aparicio C, Pastor J, Gomez-Lopez G, De Martino A, Blasco MA, Abad M, Serrano M. Tissue damage and senescence provide critical signals for cellular reprogramming in vivo. Science. 2016;354(6315):aaf4445. doi:10.1126/science.aaf4445.

    Article  PubMed  Google Scholar 

  60. Chiche A, Le Roux I, von Joest M, Sakai H, Aguin SB, Cazin C, Salam R, Fiette L, Alegria O, Flamant P, Tajbakhsh S, Li H. Injury-induced senescence enables in vivo reprogramming in skeletal muscle. Cell Stem Cell. 2017;20:407. doi:10.1016/j.stem.2016.11.020.

    Article  CAS  PubMed  Google Scholar 

  61. Ocampo A, Reddy P, Martinez-Redondo P, Platero-Luengo A, Hatanaka F, Hishida T, Li M, Lam D, Kurita M, Beyret E, Araoka T, Vazquez-Ferrer E, Donoso D, Roman JL, Xu J, Rodriguez Esteban C, Nunez G, Nunez Delicado E, Campistol JM, Guillen I, Guillen P, Izpisua Belmonte JC. In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell. 2016;167(7):1719–1733.e12. doi:10.1016/j.cell.2016.11.052.

    Article  CAS  PubMed  Google Scholar 

  62. Marion RM, Lopez de Silanes I, Mosteiro L, Gamache B, Abad M, Guerra C, Megias D, Serrano M, Blasco MA. Common telomere changes during in vivo reprogramming and early stages of tumorigenesis. Stem Cell Rep. 2017;8(2):460–75. doi:10.1016/j.stemcr.2017.01.001.

    Article  CAS  Google Scholar 

  63. Wernig M, Lengner CJ, Hanna J, Lodato MA, Steine E, Foreman R, Staerk J, Markoulaki S, Jaenisch R. A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nat Biotechnol. 2008;26(8):916–24. doi:10.1038/nbt1483.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Stadtfeld M, Maherali N, Borkent M, Hochedlinger K. A reprogrammable mouse strain from gene-targeted embryonic stem cells. Nat Methods. 2010;7(1):53–5. doi:10.1038/nmeth.1409.

    Article  CAS  PubMed  Google Scholar 

  65. de Lazaro I, Cossu G, Kostarelos K. Transient transcription factor (OSKM) expression is key towards clinical translation of in vivo cell reprogramming. EMBO Mol Med. 2017;9:733. doi:10.15252/emmm.201707650.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Stevens LC, Little CC. Spontaneous testicular teratomas in an inbred strain of mice. Proc Natl Acad Sci U S A. 1954;40(11):1080–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 2008;40(5):499–507. doi:10.1038/ng.127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Folmes CD, Nelson TJ, Martinez-Fernandez A, Arrell DK, Lindor JZ, Dzeja PP, Ikeda Y, Perez-Terzic C, Terzic A. Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab. 2011;14(2):264–71. doi:10.1016/j.cmet.2011.06.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Blackburn EH, Gall JG. A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in tetrahymena. J Mol Biol. 1978;120(1):33–53. doi:10.1016/0022-2836(78)90294-2.

    Article  CAS  PubMed  Google Scholar 

  70. Martinez P, Blasco MA. Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat Rev Cancer. 2011;11(3):161–76. doi:10.1038/nrc3025.

    Article  CAS  PubMed  Google Scholar 

  71. Marion RM, Strati K, Li H, Tejera A, Schoeftner S, Ortega S, Serrano M, Blasco MA. Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell. 2009;4(2):141–54. doi:10.1016/j.stem.2008.12.010.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Irene de Lázaro .

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de Lázaro, I. (2017). In Vivo Cell Reprogramming to Pluripotency. In: Yilmazer, A. (eds) In Vivo Reprogramming in Regenerative Medicine. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-65720-2_5

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