SpringerLink
Log in

Cloning

  • Chapter
  • First Online:
Concepts and Applications of Stem Cell Biology

Part of the book series: Learning Materials in Biosciences ((LMB))

  • 967 Accesses

Abstract

Cloning is the generation of a genetically identical organism from an existing organism. The best known example of cloning is taking plant cuttings, but also in various animals; genetically identical clones can be formed from cells or tissues, for example in some types of flatworms. Differentiation of cells in more complex animals leads to loss of developmental capacity and is caused by epigenetic events: methylation of cytosines in CpG dinucleotides and histone tail modifications. Differentiated cells can be reprogrammed to a totipotent state when introduced into an enucleated oocyte, a process known as somatic cell nuclear transfer. Although inefficient, an embryo developed with this method can give rise to offspring. The sheep Dolly was the first clone born after somatic cell nuclear transfer using an adult cell as donor. Since the birth of Dolly, several animal species have been cloned, including pets and commercially valuable animals. In therapeutic cloning, cells of a patient are injected into a human oocyte to form a blastocyst of which embryonic stem cells are generated rather than transplantation of the embryo to the uterus. These patient-specific pluripotent cells may be used for drug screening, study of the disease, or regenerative medicine.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
EUR 29.95
Price includes VAT (Germany)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
EUR 71.68
Price includes VAT (Germany)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
EUR 90.94
Price includes VAT (Germany)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Steward FC. Totipotency, variation and clonal development of cultured cells. Endeavour. 1970;29(108):117–24.

    CAS  PubMed  Google Scholar 

  2. Watts PC, Buley KR, Sanderson S, Boardman W, Ciofi C, Gibson R. Parthenogenesis in Komodo dragons. Nature. 2006;444(7122):1021–2.

    CAS  PubMed  Google Scholar 

  3. Booth W, Smith CF, Eskridge PH, Hoss SK, Mendelson JR 3rd, Schuett GW. Facultative parthenogenesis discovered in wild vertebrates. Biol Lett. 2012;8(6):983–5.

    PubMed  PubMed Central  Google Scholar 

  4. Gierer A, Berking S, Bode H, David CN, Flick K, Hansmann G, et al. Regeneration of hydra from reaggregated cells. Nat New Biol. 1972;239(91):98–101.

    CAS  PubMed  Google Scholar 

  5. Gierer A. The Hydra model - a model for what? Int J Dev Biol. 2012;56(6–8):437–45.

    PubMed  Google Scholar 

  6. Wagner DE, Wang IE, Reddien PW. Clonogenic neoblasts are pluripotent adult stem cells that underlie planarian regeneration. Science. 2011;332(6031):811–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Liu SY, Selck C, Friedrich B, Lutz R, Vila-Farre M, Dahl A, et al. Reactivating head regrowth in a regeneration-deficient planarian species. Nature. 2013;500(7460):81–4.

    CAS  PubMed  Google Scholar 

  8. Sikes JM, Newmark PA. Restoration of anterior regeneration in a planarian with limited regenerative ability. Nature. 2013;500(7460):77–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Umesono Y, Tasaki J, Nishimura Y, Hrouda M, Kawaguchi E, Yazawa S, et al. The molecular logic for planarian regeneration along the anterior-posterior axis. Nature. 2013;500(7460):73–6.

    CAS  PubMed  Google Scholar 

  10. Suzuki M, Yakushiji N, Nakada Y, Satoh A, Ide H, Tamura K. Limb regeneration in Xenopus laevis froglet. Sci World J. 2006;6(Suppl 1):26–37.

    Google Scholar 

  11. Kragl M, Knapp D, Nacu E, Khattak S, Maden M, Epperlein HH, et al. Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature. 2009;460(7251):60–5.

    CAS  PubMed  Google Scholar 

  12. Tseng AS, Adams DS, Qiu D, Koustubhan P, Levin M. Apoptosis is required during early stages of tail regeneration in Xenopus laevis. Dev Biol. 2007;301(1):62–9.

    CAS  PubMed  Google Scholar 

  13. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. King TJ, Briggs R. Changes in the nuclei of differentiating gastrula cells, as demonstrated by nuclear transplantation. Proc Natl Acad Sci U S A. 1955;41(5):321–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Hogben L. History of the Hogben test. Br Med J. 1946;2:554.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Gurdon JB, Hopwood N. The introduction of Xenopus laevis into developmental biology: of empire, pregnancy testing and ribosomal genes. Int J Dev Biol. 2000;44(1):43–50.

    CAS  PubMed  Google Scholar 

  17. 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 

  18. Gurdon JB, Uehlinger V. "Fertile" intestine nuclei. Nature. 1966;210(5042):1240–1.

    CAS  PubMed  Google Scholar 

  19. Laskey RA, Gurdon JB. Genetic content of adult somatic cells tested by nuclear transplantation from cultured cells. Nature. 1970;228(5278):1332–4.

    CAS  PubMed  Google Scholar 

  20. Illmensee K, Hoppe PC. Nuclear transplantation in Mus musculus: developmental potential of nuclei from preimplantation embryos. Cell. 1981;23(1):9–18.

    CAS  PubMed  Google Scholar 

  21. McGrath J, Solter D. Inability of mouse blastomere nuclei transferred to enucleated zygotes to support development in vitro. Science. 1984;226(4680):1317–9.

    CAS  PubMed  Google Scholar 

  22. 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.

    CAS  PubMed  Google Scholar 

  23. Willadsen SM. Nuclear transplantation in sheep embryos. Nature. 1986;320(6057):63–5.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  25. Koller BH, Hagemann LJ, Doetschman T, Hagaman JR, Huang S, Williams PJ, et al. Germ-line transmission of a planned alteration made in a hypoxanthine phosphoribosyltransferase gene by homologous recombination in embryonic stem cells. Proc Natl Acad Sci U S A. 1989;86(22):8927–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Capecchi MR. Altering the genome by homologous recombination. Science. 1989;244(4910):1288–92.

    CAS  PubMed  Google Scholar 

  27. Sims M, First NL. Production of calves by transfer of nuclei from cultured inner cell mass cells. Proc Natl Acad Sci U S A. 1994;91(13):6143–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Campbell KH, McWhir J, Ritchie WA, Wilmut I. Sheep cloned by nuclear transfer from a cultured cell line. Nature. 1996;380(6569):64–6.

    CAS  PubMed  Google Scholar 

  29. Campbell KH, Ritchie WA, Wilmut I. Nuclear-cytoplasmic interactions during the first cell cycle of nuclear transfer reconstructed bovine embryos: implications for deoxyribonucleic acid replication and development. Biol Reprod. 1993;49(5):933–42.

    CAS  PubMed  Google Scholar 

  30. Waddinngton CH. The strategy of genes: a discussion of some aspects of theoretical biology. London: George Allen and Unwin; 1957.

    Google Scholar 

  31. Berger SL. The complex language of chromatin regulation during transcription. Nature. 2007;447(7143):407–12.

    CAS  PubMed  Google Scholar 

  32. Bird A. Perceptions of epigenetics. Nature. 2007;447(7143):396–8.

    CAS  PubMed  Google Scholar 

  33. Sahin E, Depinho RA. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature. 2010;464(7288):520–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Shiels PG, Kind AJ, Campbell KH, Waddington D, Wilmut I, Colman A, et al. Analysis of telomere lengths in cloned sheep. Nature. 1999;399(6734):316–7.

    CAS  PubMed  Google Scholar 

  35. Lanza RP, Cibelli JB, Blackwell C, Cristofalo VJ, Francis MK, Baerlocher GM, et al. Extension of cell life-span and telomere length in animals cloned from senescent somatic cells. Science. 2000;288(5466):665–9.

    CAS  PubMed  Google Scholar 

  36. Jiang L, Carter DB, Xu J, Yang X, Prather RS, Tian XC. Telomere lengths in cloned transgenic pigs. Biol Reprod. 2004;70(6):1589–93.

    CAS  PubMed  Google Scholar 

  37. Wakayama S, Kohda T, Obokata H, Tokoro M, Li C, Terashita Y, et al. Successful serial recloning in the mouse over multiple generations. Cell Stem Cell. 2013;12(3):293–7.

    CAS  PubMed  Google Scholar 

  38. Vajta G. Cloning: a slee** beauty awaiting the kiss? Cell Reprogram. 2018;20(3):145–56.

    CAS  PubMed  Google Scholar 

  39. Vajta G. Handmade cloning: the future way of nuclear transfer? Trends Biotechnol. 2007;25(6):250–3.

    CAS  PubMed  Google Scholar 

  40. Shin T, Kraemer D, Pryor J, Liu L, Rugila J, Howe L, et al. A cat cloned by nuclear transplantation. Nature. 2002;415(6874):859.

    CAS  PubMed  Google Scholar 

  41. Lee BC, Kim MK, Jang G, Oh HJ, Yuda F, Kim HJ, et al. Dogs cloned from adult somatic cells. Nature. 2005;436(7051):641.

    CAS  PubMed  Google Scholar 

  42. Vogel G. Endangered species. Cloned gaur a short-lived success. Science. 2001;291(5503):409.

    CAS  PubMed  Google Scholar 

  43. Folch J, Cocero MJ, Chesne P, Alabart JL, Dominguez V, Cognie Y, et al. First birth of an animal from an extinct subspecies (Capra pyrenaica pyrenaica) by cloning. Theriogenology. 2009;71(6):1026–34.

    CAS  PubMed  Google Scholar 

  44. Wakayama S, Ohta H, Hikichi T, Mizutani E, Iwaki T, Kanagawa O, et al. Production of healthy cloned mice from bodies frozen at −20 degrees C for 16 years. Proc Natl Acad Sci U S A. 2008;105(45):17318–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Feigin CY, Newton AH, Doronina L, Schmitz J, Hipsley CA, Mitchell KJ, et al. Genome of the Tasmanian tiger provides insights into the evolution and demography of an extinct marsupial carnivore. Nat Ecol Evol. 2018;2(1):182–92.

    PubMed  Google Scholar 

  46. Woods GL, White KL, Vanderwall DK, Li GP, Aston KI, Bunch TD, et al. A mule cloned from fetal cells by nuclear transfer. Science. 2003;301(5636):1063.

    CAS  PubMed  Google Scholar 

  47. Galli C, Lagutina I, Crotti G, Colleoni S, Turini P, Ponderato N, et al. Pregnancy: a cloned horse born to its dam twin. Nature. 2003;424(6949):635.

    CAS  PubMed  Google Scholar 

  48. Church SL. Nuclear transfer saddles up. Nat Biotechnol. 2006;24(6):605–7.

    CAS  PubMed  Google Scholar 

  49. Mak TW. Gene targeting in embryonic stem cells scores a knockout in Stockholm. Cell. 2007;131(6):1027–31.

    CAS  PubMed  Google Scholar 

  50. Ezashi T, Yuan Y, Roberts RM. Pluripotent stem cells from domesticated mammals. Ann Rev Anim Biosci. 2016;4:223–53.

    CAS  Google Scholar 

  51. Niemann H, Lucas-Hahn A. Somatic cell nuclear transfer cloning: practical applications and current legislation. Reprod Domest Anim. 2012;47(Suppl 5):2–10.

    PubMed  Google Scholar 

  52. Beeson D, Lippman A. Egg harvesting for stem cell research: medical risks and ethical problems. Reprod Biomed Online. 2006;13(4):573–9.

    PubMed  Google Scholar 

  53. Noggle S, Fung HL, Gore A, Martinez H, Satriani KC, Prosser R, et al. Human oocytes reprogram somatic cells to a pluripotent state. Nature. 2011;478(7367):70–5.

    CAS  PubMed  Google Scholar 

  54. Tachibana M, Amato P, Sparman M, Gutierrez NM, Tippner-Hedges R, Ma H, et al. Human embryonic stem cells derived by somatic cell nuclear transfer. Cell. 2013;153(6):1228–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Mummery CL, Roelen BA. Stem cells: cloning human embryos. Nature. 2013;498(7453):174–5.

    CAS  PubMed  Google Scholar 

  56. Ma H, Morey R, O'Neil RC, He Y, Daughtry B, Schultz MD, et al. Abnormalities in human pluripotent cells due to reprogramming mechanisms. Nature. 2014;511(7508):177–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Liu Z, Cai Y, Wang Y, Nie Y, Zhang C, Xu Y, et al. Cloning of macaque monkeys by somatic cell nuclear transfer. Cell. 2018;172(4):881–7 e7.

    CAS  PubMed  Google Scholar 

  58. Liang P, Ding C, Sun H, **e X, Xu Y, Zhang X, et al. Correction of beta-thalassemia mutant by base editor in human embryos. Protein Cell. 2017;8(11):811–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Prainsack B, Cherkas LF, Spector TD. Attitudes towards human reproductive cloning, assisted reproduction and gene selection: a survey of 4600 British twins. Hum Reprod. 2007;22(8):2302–8.

    CAS  PubMed  Google Scholar 

  60. Gomez MC, Pope CE, Giraldo A, Lyons LA, Harris RF, King AL, et al. Birth of African wildcat cloned kittens born from domestic cats. Cloning Stem Cells. 2004;6(3):247–58.

    CAS  PubMed  Google Scholar 

  61. Wani NA, Vettical BS, Hong SB. First cloned Bactrian camel (Camelus bactrianus) calf produced by interspecies somatic cell nuclear transfer: a step towards preserving the critically endangered wild Bactrian camels. PLoS One. 2017;12(5):e0177800.

    PubMed  PubMed Central  Google Scholar 

  62. Zhou Q, Renard JP, Le Friec G, Brochard V, Beaujean N, Cherifi Y, et al. Generation of fertile cloned rats by regulating oocyte activation. Science. 2003;302(5648):1179.

    CAS  PubMed  Google Scholar 

  63. Kato Y, Tani T, Sotomaru Y, Kurokawa K, Kato J, Doguchi H, et al. Eight calves cloned from somatic cells of a single adult. Science. 1998;282(5396):2095–8.

    CAS  PubMed  Google Scholar 

  64. Hwang I, Jeong YW, Kim JJ, Lee HJ, Kang M, Park KB, et al. Successful cloning of coyotes through interspecies somatic cell nuclear transfer using domestic dog oocytes. Reprod Fertil Dev. 2013;25(8):1142–8.

    PubMed  Google Scholar 

  65. Wani NA, Wernery U, Hassan FA, Wernery R, Skidmore JA. Production of the first cloned camel by somatic cell nuclear transfer. Biol Reprod. 2010;82(2):373–9.

    CAS  PubMed  Google Scholar 

  66. Loi P, Ptak G, Barboni B, Fulka J Jr, Cappai P, Clinton M. Genetic rescue of an endangered mammal by cross-species nuclear transfer using post-mortem somatic cells. Nat Biotechnol. 2001;19(10):962–4.

    CAS  PubMed  Google Scholar 

  67. Li Z, Sun X, Chen J, Liu X, Wisely SM, Zhou Q, et al. Cloned ferrets produced by somatic cell nuclear transfer. Dev Biol. 2006;293(2):439–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Lanza RP, Cibelli JB, Diaz F, Moraes CT, Farin PW, Farin CE, et al. Cloning of an endangered species (Bos gaurus) using interspecies nuclear transfer. Cloning. 2000;2(2):79–90.

    CAS  PubMed  Google Scholar 

  69. Baguisi A, Behboodi E, Melican DT, Pollock JS, Destrempes MM, Cammuso C, et al. Production of goats by somatic cell nuclear transfer. Nat Biotechnol. 1999;17(5):456–61.

    CAS  PubMed  Google Scholar 

  70. Wakayama T, Perry AC, Zuccotti M, Johnson KR, Yanagimachi R. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature. 1998;394(6691):369–74.

    CAS  PubMed  Google Scholar 

  71. Onishi A, Iwamoto M, Akita T, Mikawa S, Takeda K, Awata T, et al. Pig cloning by microinjection of fetal fibroblast nuclei. Science. 2000;289(5482):1188–90.

    CAS  PubMed  Google Scholar 

  72. Polejaeva IA, Chen SH, Vaught TD, Page RL, Mullins J, Ball S, et al. Cloned pigs produced by nuclear transfer from adult somatic cells. Nature. 2000;407(6800):86–90.

    CAS  PubMed  Google Scholar 

  73. Chesne P, Adenot PG, Viglietta C, Baratte M, Boulanger L, Renard JP. Cloned rabbits produced by nuclear transfer from adult somatic cells. Nat Biotechnol. 2002;20(4):366–9.

    CAS  PubMed  Google Scholar 

  74. Berg DK, Li C, Asher G, Wells DN, Oback B. Red deer cloned from antler stem cells and their differentiated progeny. Biol Reprod. 2007;77(3):384–94.

    CAS  PubMed  Google Scholar 

  75. Gomez MC, Pope CE, Kutner RH, Ricks DM, Lyons LA, Ruhe M, et al. Nuclear transfer of sand cat cells into enucleated domestic cat oocytes is affected by cryopreservation of donor cells. Cloning Stem Cells. 2008;10(4):469–83.

    CAS  PubMed  Google Scholar 

  76. Shi D, Lu F, Wei Y, Cui K, Yang S, Wei J, et al. Buffalos (Bubalus bubalis) cloned by nuclear transfer of somatic cells. Biol Reprod. 2007;77(2):285–91.

    CAS  PubMed  Google Scholar 

  77. Kim MK, Jang G, Oh HJ, Yuda F, Kim HJ, Hwang WS, et al. Endangered wolves cloned from adult somatic cells. Cloning Stem Cells. 2007;9(1):130–7.

    CAS  PubMed  Google Scholar 

  78. Jansen DL, Edwards ML, Koster JA, Lanza RP, Ryder OA. Postnatal management of cryptorchid Banteng calves cloned by nuclear transfer utilizing frozen fibroblast cultures and enucleated cow ova. Reprod Fertil Dev. 2004;16:206.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Embryology, Anatomy and Physiology, Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht Universtity, Utrecht, The Netherlands

    Bernard A. J. Roelen

Authors
  1. Bernard A. J. Roelen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernard A. J. Roelen .

Editor information

Editors and Affiliations

  1. Centro de Ecologia, Evolução e Alterações Ambientais, Departamento de Biologia Animal, Faculdade de Ciências da, Universidade de Lisboa, Lisbon, Portugal

    Gabriela Rodrigues

  2. Embryology, Anatomy and Physiology, Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht Universtity, Utrecht, The Netherlands

    Bernard A. J. Roelen

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Roelen, B.A.J. (2020). Cloning. In: Rodrigues, G., Roelen, B.A.J. (eds) Concepts and Applications of Stem Cell Biology. Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-030-43939-2_6

Download citation

Publish with us

Policies and ethics

Search

Navigation