Skip to main content

Cell Fusion-Mediated Nuclear Reprogramming of Somatic Cells

  • Chapter
  • First Online:
  • 1170 Accesses

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

Abstract

Epigenetic reprogramming of nuclei from differentiated to pluripotent state can be induced by three experimental approaches: nuclear transfer, cell fusion, and transduction of transcription factors. In cell fusion between embryonic stem and somatic cells, stem cell-derived trans-acting factors function to confer pluripotency on somatic cell nuclei by overwriting the epigenotype of the undifferentiated state. Intensive analyses using inter-subspecific hybrid cells revealed that de-­condensation of nuclear chromatin is a key initial step for acquiring a fully reprogrammed nuclear status. The formation of de-condensed chromatin is a common molecular event seen in cell fusion-mediated reprogramming and the generation of induced pluripotent stem cells via the transduction of transcription factors. Thus, cell fusion is a powerful tool for providing information on the molecular mechanisms of nuclear reprogramming.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM et al (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968–973

    Article  PubMed  CAS  Google Scholar 

  • Bhutani N, Brady JJ, Damian M et al (2010) Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 463:1042–1047

    Article  PubMed  CAS  Google Scholar 

  • Blau HM, Pavlath GK, Hardeman EC et al (1985) Plasticity of the differentiated state. Science 230:758–766

    Article  PubMed  CAS  Google Scholar 

  • Briggs R, King TJ (1952) Transplantation of living nuclei from blastula cells into enucleated frog’s eggs. Proc Natl Acad Sci USA 38:455–464

    Article  PubMed  CAS  Google Scholar 

  • Brons IG, Smithers LE, Trotter MW et al (2007) Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448:191–195

    Article  PubMed  CAS  Google Scholar 

  • Cowan CA, Atienza J, Melton DA et al (2005) Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309:1369–1373

    Article  PubMed  CAS  Google Scholar 

  • Davidson RL, Ephrussi B, Yamamoto K (1966) Regulation of pigment synthesis in mammalian cells, as studied by somatic hybridization. Proc Natl Acad Sci USA 56:1437–1440

    Article  PubMed  CAS  Google Scholar 

  • Evans MJ, Kaufman MH (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154–156

    Article  PubMed  CAS  Google Scholar 

  • Gurdon J (1962) The developmental capacity of nuclei taken from intestinal epithelial cells of feeding tadpoles. J Embryol Exp Morphol 10:622–640

    PubMed  CAS  Google Scholar 

  • Han DW, Do JT, Gentile L et al (2008) Pluripotential reprogramming of the somatic genome in hybrid cells occurs with the first cell cycle. Stem Cells 26:445–454

    Article  PubMed  CAS  Google Scholar 

  • Harris H (1965) Behaviour of differentiated nuclei in heterokaryons of animal cells from different species. Nature 206:583–588

    Article  PubMed  CAS  Google Scholar 

  • Harris H, Watkins JF (1965) Hybrid cells derived from mouse and man: artificial heterokaryons of mammalian cells from different species. Nature 205:640–646

    Article  PubMed  CAS  Google Scholar 

  • Hatano S, Tada M, Kimura H et al (2005) Pluripotential competence of cells associated with Nanog activity. Mech Dev 122:67–79

    Article  PubMed  CAS  Google Scholar 

  • Kanatsu-Shinohara M, Inoue K, Lee J et al (2004) Generation of pluripotent stem cells from ­neonatal mouse testis. Cell 119:1001–1012

    Article  PubMed  CAS  Google Scholar 

  • Kao KN, Miehayluk M (1974) A Method for high-frequency intergeneric fusion of plant protoplasts. Planta 115:355–367

    Article  CAS  Google Scholar 

  • Killary AM, Fournier RE (1984) A genetic analysis of extinction: trans-dominant loci regulate expression of liver-specific traits in hepatoma hybrid cells. Cell 38:523–534

    Article  PubMed  CAS  Google Scholar 

  • Kimura H, Tada M, Nakatsuji N et al (2004) Histone code modifications on pluripotential nuclei of reprogrammed somatic cells. Mol Cell Biol 24:5710–5720

    Article  PubMed  CAS  Google Scholar 

  • Lluis F, Pedone E, Pepe S et al (2008) Periodic activation of Wnt/beta-catenin signaling enhances somatic cell reprogramming mediated by cell fusion. Cell Stem Cell 3:493–507

    Article  PubMed  CAS  Google Scholar 

  • Matsui Y, Zsebo K, Hogan BL (1992) Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell 70:841–847

    Article  PubMed  CAS  Google Scholar 

  • Matsumura H, Tada T (2008) Cell fusion-mediated nuclear reprogramming of somatic cells. Reprod Biomed Online 16:51–56

    Article  PubMed  Google Scholar 

  • Matsumura H, Tada M, Otsuji T et al (2007) Targeted chromosome elimination from ES-somatic hybrid cells. Nat Methods 4:23–25

    Article  PubMed  CAS  Google Scholar 

  • Mikkelsen TS, Hanna J, Zhang X et al (2008) Dissecting direct reprogramming through integrative genomic analysis. Nature 454:49–55

    Article  PubMed  CAS  Google Scholar 

  • Miller RA, Ruddle FH (1976) Pluripotent teratocarcinoma-thymus somatic cell hybrids. Cell 9:45–55

    Article  PubMed  CAS  Google Scholar 

  • Mills AA, Bradley A (2001) From mouse to man: generating megabase chromosome rearrangements. Trends Genet 17:331–339

    Article  PubMed  CAS  Google Scholar 

  • Mitsui K, Tokuzawa Y, Itoh H et al (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 

  • Nagata S, Toyoda M, Yamaguchi S et al (2009) Efficient reprogramming of human and mouse primary extra-embryonic cells to pluripotent stem cells. Genes Cells 14:1395–1404

    Article  PubMed  CAS  Google Scholar 

  • Nakamura T, Inoue K, Ogawa S et al (2008) Effects of Akt signaling on nuclear reprogramming. Genes Cells 13:1269–1277

    Article  PubMed  CAS  Google Scholar 

  • Okada Y, Suzuki T, Hosaka Y (1957) Interaction between influenza virus and Ehrlich’s tumor cells III. Fusion phenomenon of Ehrlich’s tumor cell by the action of HVJ Z strain. Med J Osaka Univ 7:709–717

    Google Scholar 

  • Schneider JA, Weiss MC (1971) Expression of differentiated functions in hepatoma cell hybrids I. Tyrosine aminotransferase in hepatoma-fibroblast hybrids. Proc Natl Acad Sci USA 68:127–131

    Article  PubMed  CAS  Google Scholar 

  • Suemori H, Yasuchika K, Hasegawa K et al (2006) Efficient establishment of human embryonic stem cell lines and long-term maintenance with stable karyotype by enzymatic bulk passage. Biochem Biophys Res Commun 345:926–932

    Article  PubMed  CAS  Google Scholar 

  • Tada T (2008) Genetic modification-free reprogramming to induced pluripotent cells: fantasy or reality? Cell Stem Cell 3:121–122

    Article  PubMed  CAS  Google Scholar 

  • Tada T, Tada M (2001) Toti-/pluripotential stem cells and epigenetic modifications. Cell Struct Funct 26:149–160

    Article  PubMed  CAS  Google Scholar 

  • Tada M, Tada T (2006) Nuclear reprogramming of somatic nucleus hybridized with embryonic stem cells by electrofusion. Methods Mol Biol 329:411–420

    PubMed  Google Scholar 

  • Tada M, Tada T, Lefebvre L et al (1997) Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells. EMBO J 16:6510–6520

    Article  PubMed  CAS  Google Scholar 

  • Tada M, Takahama Y, Abe K et al (2001) Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Biol 11:1553–1558

    Article  PubMed  CAS  Google Scholar 

  • Tada M, Morizane A, Kimura H et al (2003) Pluripotency of reprogrammed somatic genomes in embryonic stem hybrid cells. Dev Dyn 227:504–510

    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 et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  PubMed  CAS  Google Scholar 

  • Tanaka S, Kunath T, Hadjantonakis AK et al (1998) Promotion of trophoblast stem cell proliferation by FGF4. Science 282:2072–2075

    Article  PubMed  CAS  Google Scholar 

  • Tesar PJ, Chenoweth JG, Brook FA et al (2007) New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448:196–199

    Article  PubMed  CAS  Google Scholar 

  • Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  PubMed  CAS  Google Scholar 

  • Wakayama S, Ohta H, Hikichi T et al (2008) Production of healthy cloned mice from bodies frozen at −20 degrees C for 16 years. Proc Natl Acad Sci USA 105:17318–17322

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Willenbring H, Akkari Y et al (2003) Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422:897–901

    Article  PubMed  CAS  Google Scholar 

  • Weimann JM, Johansson CB, Trejo A et al (2003) Stable reprogrammed heterokaryons form spontaneously in Purkinje neurons after bone marrow transplant. Nat Cell Biol 5:959–966

    Article  PubMed  CAS  Google Scholar 

  • Wilmut I, Schnieke AE, McWhir J et al (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385:810–813

    Article  PubMed  CAS  Google Scholar 

  • Yu J, Vodyanik MA, He P et al (2006) Human embryonic stem cells reprogram myeloid precursors following cell-cell fusion. Stem Cells 24:168–176

    Article  PubMed  Google Scholar 

  • Yu J, Vodyanik MA, Smuga-Otto K et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann U, Scheurich P (1981) High frequency fusion of plant protoplasts by electric fields. Planta 151:26–32

    Article  Google Scholar 

Download references

Acknowledgment

Mr. K. Hirano is a research fellow of the Japanese Society for the Promotion of Science.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takashi Tada .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Hirano, K., Tada, T. (2011). Cell Fusion-Mediated Nuclear Reprogramming of 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_6

Download citation

Publish with us

Policies and ethics