Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Biological implications of cell fusion

Nature Reviews Molecular Cell Biology volume 6, pages 567–575 (2005)Cite this article

Key Points

  • Fusion of one or more cells can occur during development as well as in mature individuals. Fusion of two or more cells of the same type yields a syncytium. Syncytia are commonly found in placenta, bone, cartilage, muscle and multi-nucleated giant cells.

  • Fusion of two or more cells of different types can yield multi-nucleated cells called heterokaryons. Heterokaryons have been observed after cells of bone marrow origin fused with hepatocytes, cardiomyocytes and Purkinje neurons to form multi-nucleated cells.

  • Fusion of two or more cells of the same or different type and fusion of nuclei can yield synkaryons. Synkaryons have been found among hepatocytes, kidney tubules and B cells.

  • Cell fusion can cause a change in the phenotype and/or the function of cells. Cell fusion could therefore explain transdifferentiation of committed somatic cells.

  • Cell fusion can reverse or repair injury to tissues. In this context, cell fusion facilitates the regeneration of tissues.

  • Cell fusion can promote the transmission of viruses. Fusion of cells of individuals of disparate species might explain the transmission of viruses between species and the genesis of new pathogens.

  • Cell fusion and nuclear fusion that occur in the formation of synkaryons can allow the re-sorting and recombination of chromosomal DNA. Fusion of nuclei of an immature cell, such as a stem cell, and a mature cell might generate proliferation and malignancy.

Abstract

Until recently, cells were thought to be integral and discrete components of tissues, and their state was determined by cell differentiation. However, under some conditions, stem cells or their progeny can fuse with cells of other types, mixing cytoplasmic and even genetic material of different (heterotypic) origins. The fusion of heterotypic cells could be of central importance for development, repair of tissues and the pathogenesis of disease.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Cells derived by fusion.
Figure 2: The stalk-pore model of cell fusion.
Figure 3: Two methods to identify cell fusion as an antecedent event.
Figure 4: The karyotype of synkaryons formed in vivo.
Figure 5: Role of synkaryons in disease.

Similar content being viewed by others

References

  1. Hooke, R. Micrographia: or some Physiological Descriptions of Minute Bodies made by Magnifying Glasses with Observations and Inquiries thereupon. (J. Martyn and J. Allestry, London, 1665).

    Book  Google Scholar 

  2. van Leeuwenhoek, A. The Collected Letters of Antoni van Leeuwenhoek. (Swetz & Zeitlinger, Amsterdam, 1939–1967).

    Google Scholar 

  3. Baker, J. R. The cell theory: a restatement, history and critique. Part IV. The multiplication of cells. Q. J. Microsc. Sci. 94, 407–440 (1953).

    Google Scholar 

  4. Schleiden, M. J. Beitrage zur Phytogenesis. Arch. Anat. Physiol. 137–176 (1838).

  5. Schwann, T. Mikroskopische Untersuchungen uber die Ubereinstimmung in der Struktur und dem Wachsten der Thiere und Pflanzen. (Saunderschen Buchhandlung, Berlin, 1839).

    Google Scholar 

  6. Wolpert, L. The evolution of 'the cell theory'. Curr. Biol. 6, 225–228 (1996).

    Article  CAS  PubMed  Google Scholar 

  7. Huppertz, B., Frank, H. G., Kingdom, J. C., Reister, F. & Kaufmann, P. Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta. Histochem. Cell Biol. 110, 495–508 (1998).

    Article  CAS  PubMed  Google Scholar 

  8. Vignery, A. Osteoclasts and giant cells: macrophage–macrophage fusion mechanism. Int. J. Exp. Pathol. 81, 291–304 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kahn, A. J., Teitelbaum, S. L., Malone, J. D. & Krukowski, M. The relationship of monocytic cells to the differentiation and resorption of bone. Prog. Clin. Biol. Res. B. 110, 239–248 (1982).

    Google Scholar 

  10. Loutit, J. F. & Nisbet, N. W. The origin of osteoclasts. Immunobiology 161, 193–203 (1982).

    Article  CAS  PubMed  Google Scholar 

  11. Huppertz, B., Tews, D. S. & Kaufmann, P. Apoptosis and syncytial fusion in human placental trophoblast and skeletal muscle. Int. Rev. Cytol. 205, 215–253 (2001).

    Article  CAS  PubMed  Google Scholar 

  12. Taylor, M. V. Muscle development: molecules of myoblast fusion. Curr. Biol. 10, R646–R648 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Harris, H. & Watkins, J. F. Hybrid cells derived from mouse and man: artificial heterokaryons of mammalian cells from different species. Nature 205, 640–646 (1965). Sendai virus was used to fuse murine Ehrlich ascites cells and human HeLa cells in vitro . The cells formed by fusion were heterokaryons that remained stable over time and exhibited functions and a phenotype that was distinct from either fusion partner. This paper was the first to report the distinct properties of heterokaryons.

    Article  CAS  PubMed  Google Scholar 

  14. Harris, H., Sidebottom, E., Grace, D. M. & Bramwell, M. E. The expression of genetic information: a study with hybrid animal cells. J. Cell Sci. 4, 499–525 (1969).

    CAS  PubMed  Google Scholar 

  15. Ringertz, N. R., Carlsson, S. A., Ege, T. & Bolund, L. Detection of human and chick nuclear antigens in nuclei of chick erythrocytes during reactivation in heterokaryons with HeLa cells. Proc. Natl Acad. Sci. USA 68, 3228–3232 (1971).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Carlsson, S. A., Luger, O., Ringertz, N. R. & Savage, R. E. Phenotypic expression in chick erythrocyte x rat myoblast hybrids and in chick myoblast x rat myoblast hybrids. Exp. Cell Res. 84, 47–55 (1974).

    Article  CAS  PubMed  Google Scholar 

  17. Lawrence, J. B. & Coleman, J. R. Extinction of muscle-specific properties in somatic cell heterokaryons. Dev. Biol. 101, 463–476 (1984).

    Article  CAS  PubMed  Google Scholar 

  18. Wright, W. E. & Aronoff, J. The suppression of myogenic functions in heterokaryons formed by fusing chick myocytes to diploid rat fibroblasts. Cell Differ. 12, 299–306 (1983).

    Article  CAS  PubMed  Google Scholar 

  19. Konieczny, S. F., Lawrence, J. B. & Coleman, J. R. Analysis of muscle protein expression in polyethylene glycol-induced chicken: rat myoblast heterokaryons. J. Cell Biol. 97, 1348–1355 (1983).

    Article  CAS  PubMed  Google Scholar 

  20. Ringertz, N. R. & Savage, R. E. Cell Hybrids (Academic Press, New York, 1976).

    Google Scholar 

  21. Blau, H. M. & Blakely, B. T. Plasticity of cell fate: insights from heterokaryons. Sem.Cell Dev. Biol. 10, 267–272 (1999).

    Article  CAS  Google Scholar 

  22. Terada, N. et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416, 542–545 (2002).

    Article  CAS  PubMed  Google Scholar 

  23. Ying, Q. L., Nichols, J., Evans, E. P. & Smith, A. G. Changing potency by spontaneous fusion. Nature 416, 545–548 (2002). Neuronal stem cells were fused with embryonic stem cells and the fused cells injected into murine blastocysts. The fused cells acquired tissue-specific properties and differentiation potential in the hosts. These authors suggest that cell fusion could account for transdifferentiation.

    Article  CAS  PubMed  Google Scholar 

  24. Gibson, A. J. et al. Dermal fibroblasts convert to a myogenic lineage in mdx mouse muscle. J. Cell Sci. 108, 207–214 (1995). The authors transplanted dermal fibroblasts into mice with defective myotubes and found that the fibroblasts fused with myotubes. This study was the first to show that fusion of cells can contribute to the regeneration of tissues.

    CAS  PubMed  Google Scholar 

  25. Gussoni, E. et al. Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. J. Clin. Invest. 110, 807–814 (2002). Describes a human patient with Duchenne muscular dystrophy who received a bone marrow transplant. The bone marrow cells fused with skeletal muscle cells to yield heterokaryons. This paper is the first report of heterokaryon formation in a human subject.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang, X. et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422, 897–900 (2003). Bone-marrow-derived cells were shown to fuse with hepatocytes to repair liver damage. This paper shows that cell fusion can contribute to the regeneration of a parenchymal organ and that fusion can eventuate reduction division.

    Article  CAS  PubMed  Google Scholar 

  27. Vassilopoulos, G., Wang, P. R. & Russell, D. W. Transplanted bone marrow regenerates liver by cell fusion. Nature 422, 901–904 (2003).

    Article  CAS  PubMed  Google Scholar 

  28. Weimann, J. M., Johansson, C. B., Trejo, A. & Blau, H. M. Stable reprogrammed heterokaryons form spontaneously in Purkinje neurons after bone marrow transplant. Nature Cell Biol. 5, 959–966 (2003).

    Article  CAS  PubMed  Google Scholar 

  29. Alvarez-Dolado, M. et al. Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425, 968–973 (2003). Bone-marrow-derived cells were shown to fuse with hepatocytes, Purkinje neurons and cardiac muscle cells to yield heterokaryons in mice. The studies were done in healthy mice that had not suffered tissue injury, which raises the possibility that cell fusion can contribute to the development and maintenance of certain tissues.

    Article  CAS  PubMed  Google Scholar 

  30. Pomerantz, J. & Blau, H. M. Nuclear reprogramming: a key to stem cell function in regenerative medicine. Nature Cell Biol. 6, 810–816 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Tsai, R. Y., Kittappa, R. & McKay, R. D. Plasticity, niches, and the use of stem cells. Dev. Cell 2, 707–712 (2002).

    Article  CAS  PubMed  Google Scholar 

  32. Alison, M. R. et al. Recipes for adult stem cell plasticity: fusion cuisine or readymade? J. Clin. Pathol. 57, 113–120 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ogle, B. M. et al. Spontaneous fusion of cells between species yields transdifferentiation and retroviral in vivo. FASEB J. 18, 548–550 (2004). Human bone marrow cells were engrafted into fetal pigs that after birth contained synkaryons with both porcine and human DNA. The synkaryons had porcine endogenous retrovirus that could be transmitted to human cells. This study shows how cell fusion can transfer viruses from one species to another.

    Article  CAS  PubMed  Google Scholar 

  34. Barski, G., Sorieul, S. & Cornefert, F. Production dans des cultures in vitro de deux souches cellulaires en association de cellules de caratere hybride. C. R. Hebd. Seances Acad. des Sci. 251, 1825–1827 (1960). When cells of two different tumour lines are mixed in culture, approximately 30% of one cell type fuse with the other to yield a cell with a single hybrid nucleus. This study was the first to report the fusion of cells and the fusion of nuclei in vitro.

    CAS  Google Scholar 

  35. Kohler, G. & Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495–497 (1975).

    Article  CAS  PubMed  Google Scholar 

  36. Hernandez, L. D., Hoffman, L. R., Wolfsberg, T. G. & White, J. M. Virus–cell and cell–cell fusion. Annu. Rev. Cell Dev. Biol. 12, 627–661 (1996).

    Article  CAS  PubMed  Google Scholar 

  37. Kozlov, M. M. & Markin, V. S. Possible mechanism of membrane fusion. Biofizika 28, 242–247 (1983) (in Russian).

    CAS  PubMed  Google Scholar 

  38. Leikina, E. & Chernomordik, L. V. Reversible merger of membranes at the early stage of influenza hemagglutinin-mediated fusion. Mol. Biol. Cell 11, 2359–2371 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yang, L. & Huang, H. W. Observation of a membrane fusion intermediate structure. Science 297, 1877–1879 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Chernomordik, L., Kozlov, M. M. & Zimmerberg, J. Lipids in biological membrane fusion. J. Membr. Biol. 146, 1–14 (1995).

    Article  CAS  PubMed  Google Scholar 

  41. Chernomordik, L. V. & Kozlov, M. M. Protein–lipid interplay in fusion and fission of biological membranes. Annu. Rev. Biochem. 72, 175–207 (2003).

    Article  CAS  PubMed  Google Scholar 

  42. Muller, M., Katsov, K. & Schick, M. A new mechanism of model membrane fusion determined from Monte Carlo simulation. Biophys. J. 85, 1611–1623 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Katsov, K., Muller, M. & Schick, M. Field theoretic study of bilayer membrane fusion. I. Hemifusion mechanism. Biophys. J. 87, 3277–3290 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Shemer, G. & Podbilewicz, B. The story of cell fusion: big lessons from little worms. BioEssays 25, 672–682 (2003). This paper provides an authoritative review of the mechanics of cell fusion.

    Article  PubMed  Google Scholar 

  45. Blond, J. L. et al. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J. Virol. 74, 3321–3329 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mi, S. et al. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403, 785–789 (2000).

    Article  CAS  PubMed  Google Scholar 

  47. Inoue, N., Ikawa, M., Isotani, A. & Okabe, M. The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. Nature 434, 234–238 (2005).

    Article  CAS  PubMed  Google Scholar 

  48. Gilpin, B. J. et al. A novel, secreted form of human ADAM12 (meltrin-α) provokes myogenesis in vivo. J. Biol. Chem. 273, 157–166 (1998).

    Article  CAS  PubMed  Google Scholar 

  49. Galliano, M. F. et al. Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, α-actinin-2, is required for myoblast fusion. J. Biol. Chem. 275, 13933–13939 (2000).

    Article  CAS  PubMed  Google Scholar 

  50. Makino, S. et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J. Clin. Invest. 103, 697–705 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Cho, C., Turner, L., Primakoff, P. & Myles, D. G. Genomic organization of the mouse fertilin β gene that encodes an ADAM family protein active in sperm–egg fusion. Dev. Genet. 20, 320–328 (1997).

    Article  CAS  PubMed  Google Scholar 

  52. Evans, J. P., Schultz, R. M. & Kopf, G. S. Roles of the disintegrin domains of mouse fertilins α and β in fertilization. Biol. Reprod. 59, 145–152 (1998).

    Article  CAS  PubMed  Google Scholar 

  53. Primakoff, P. & Myles, D. G. The ADAM gene family: surface proteins with adhesion and protease activity. Trends Genet. 16, 83–87 (2000).

    Article  CAS  PubMed  Google Scholar 

  54. Blumenthal, R., Clague, M. J., Durell, S. R. & Epand, R. M. Membrane fusion. Chem. Rev. 103, 53–69 (2003).

    Article  CAS  PubMed  Google Scholar 

  55. Nishikawa, S. et al. Nep98p is a component of the yeast spindle pole body and essential for nuclear division and fusion. J. Biol. Chem. 278, 9938–9943 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. Bucci, M. & Wente, S. R. In vivo dynamics of nuclear pore complexes in yeast. J. Cell Biol. 136, 1185–1199 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Rose, M. D. Nuclear fusion in the yeast Saccharomyces cerevisiae. Annu. Rev. Cell Dev. Biol. 12, 663–695 (1996).

    Article  CAS  PubMed  Google Scholar 

  58. Chen, Y., Zhang, L., Zhou, Y., Geng, Y. & Chen, Z. Inducing somatic meiosis-like reduction at high frequency by caffeine in root-tip cells of Vicia faba. Mutat. Res. 452, 67–72 (2000).

    Article  CAS  PubMed  Google Scholar 

  59. Brinkley, B. R. Managing the centrosome numbers game: from chaos to stability in cancer cell division. Trends Cell Biol. 11, 18–21 (2001).

    Article  CAS  PubMed  Google Scholar 

  60. Mohler, W. A. et al. The type I membrane protein EFF-1 is essential for developmental cell fusion. Dev. Cell 2, 355–362 (2002).

    Article  CAS  PubMed  Google Scholar 

  61. Bernirschke, K. & Kaufmann, P. Pathology of the Human Placenta (Springer, New York, 2000).

    Book  Google Scholar 

  62. Hoshina, M., Boothby, M. & Boime, I. Cytological localization of chorionic gonadotropin α and placental lactogen mRNAs during development of the human placenta. J. Cell Biol. 93, 190–198 (1982).

    Article  CAS  PubMed  Google Scholar 

  63. Hoshina, M., Boime, I. & Mochizuki, M. Cytological localization of hPL, hCG, and mRNA in chorionic tissue using in situ hybridization. Nippon Sanka Fujinka Gakkai Zasshi 36, 397–404 (1984).

    CAS  PubMed  Google Scholar 

  64. Johansen, M., Redman, C. W., Wilkins, T. & Sargent, I. L. Trophoblast deportation in human pregnancy — its relevance for pre-eclampsia. Placenta 20, 531–539 (1999).

    Article  CAS  PubMed  Google Scholar 

  65. Redman, C. W. & Sargent, I. L. Placental debris, oxidative stress and pre-eclampsia. Placenta 21, 597–602 (2000).

    Article  CAS  PubMed  Google Scholar 

  66. Blau, H. M., Chiu, C. P. & Webster, C. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell 32, 1171–1180 (1983).

    Article  CAS  PubMed  Google Scholar 

  67. Blau, H. M. Stem-cell fusion: a twist of fate. Nature 419, 437 (2002).

    Article  CAS  PubMed  Google Scholar 

  68. Weimann, J. M., Charlton, C. A., Brazelton, T. R., Hackman, R. C. & Blau, H. M. Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains. Proc. Natl Acad. Sci. USA 100, 2088–2093 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. van Bekkum, D. W. Phylogenetic aspects of tissue regeneration: role of stem cells. A concise overview. Blood Cells Mol. Dis. 32, 11–16 (2004).

    CAS  PubMed  Google Scholar 

  70. Relvas, J. B., Aldridge, H., Wells, K. E., Wells, D. J. & Watt, D. J. Exogenous genes are expressed in mdx muscle fibres following implantation of primary mouse skin cells. Basic App. Myol. 7, 211–219 (1997).

    Google Scholar 

  71. Ferrari, G. et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279, 1528–1530 (1998).

    Article  CAS  PubMed  Google Scholar 

  72. Bittner, R. E. et al. Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat. Embryol. (Berl.) 199, 391–396 (1999).

    Article  CAS  Google Scholar 

  73. Gussoni, E. et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401, 390–394 (1999).

    CAS  PubMed  Google Scholar 

  74. Nygren, J. M. et al. Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nature Med. 10, 494–501 (2004).

    Article  CAS  PubMed  Google Scholar 

  75. Balsam, L. B. et al. Hematopoietic stem cells adopt mature hematopoietic fates in ischemic myocardium. Nature 428, 668–673 (2004).

    Article  CAS  PubMed  Google Scholar 

  76. Murry, C. E. et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 428, 664–668 (2004).

    Article  CAS  PubMed  Google Scholar 

  77. Deb, A. et al. Bone marrow-derived cardiomyocytes are present in adult human heart: a study of gender-mismatched bone marrow transplantation patients. Circulation 107, 1247–1249 (2003).

    Article  PubMed  Google Scholar 

  78. Quaini, F. et al. Chimerism of the transplanted heart. N. Engl. J. Med. 346, 5–15 (2002).

    Article  PubMed  Google Scholar 

  79. Poulsom, R., Alison, M. R., Forbes, S. J. & Wright, N. A. Adult stem cell plasticity. J. Pathol. 197, 441–456 (2002).

    Article  PubMed  Google Scholar 

  80. Ianus, A., Holz, G. G., Theise, N. D. & Hussain, M. A. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J. Clin. Invest. 111, 843–850 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Camargo, F. D., Green, R., Capetenaki, Y., Jackson, K. A. & Goodell, M. A. Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nature Med. 9, 1520–1527 (2003).

    Article  CAS  PubMed  Google Scholar 

  82. Camargo, F. D., Finegold, M. & Goodell, M. A. Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners. J. Clin. Invest. 113, 1266–1270 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Willenbring, H. et al. Myelomonocytic cells are sufficient for therapeutic cell fusion in liver. Nature Med. 10, 744–748 (2004).

    Article  CAS  PubMed  Google Scholar 

  84. Chapman, L. E. et al. Xenotransplantation and xenogeneic infections. N. Eng. J. Med. 333, 1498–1501 (1995).

    Article  CAS  Google Scholar 

  85. Patience, C., Takeuchi, Y. & Weiss, R. A. Infection of human cells by an endogenous retrovirus of pigs. Nature Med. 3, 282–286 (1997).

    Article  CAS  PubMed  Google Scholar 

  86. Paradis, K. et al. Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. Science 285, 1236–1241 (1999).

    Article  CAS  PubMed  Google Scholar 

  87. Urnovitz, H. B. & Murphy, W. H. Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease. Clin. Microbiol. Rev. 9, 72–99 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Goldenberg, D. M., Pavia, R. A. & Tsao, M. C. In vivo hybridisation of human tumour and normal hamster cells. Nature 250, 649–651 (1974).

    Article  CAS  PubMed  Google Scholar 

  89. Condamine, H., Custer, R. P. & Mintz, B. Pure-strain and genetically mosaic liver tumors histochemically identified with the-glucuronidase marker in allophenic mice. Proc. Natl Acad. Sci. USA 68, 2032–2036 (1971).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Houghton, J. et al. Gastric cancer originating from bone marrow-derived cells. Science 306, 1568–1571 (2004). Reports that transplanted bone marrow cells can promote the formation of Helicobacter felis -induced gastric epithelial cancers in mice. A possible interpretation is that the bone marrow cells fused with gastric epithelium to yield synkaryons with genomic instability and that the synkaryons became tumorigenic.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Work in the authors' laboratory is supported by grants from the National Institutes of Health.

Author information

Authors and Affiliations

  1. Transplantation Biology and the Department of Physiology, Mayo Clinic, 200 First Street SW, Medical Sciences 2-66, Rochester, 55905, Minnesota, USA

    Brenda M. Ogle

  2. Transplantation Biology and the Department of Immunology, Mayo Clinic, 200 First Street SW, Medical Sciences 2-66, Rochester, 55905, Minnesota, USA

    Marilia Cascalho & Jeffrey L. Platt

  3. Transplantation Biology and the Department of Pediatrics, Mayo Clinic, 200 First Street SW, Medical Sciences 2-66, Rochester, 55905, Minnesota, USA

    Marilia Cascalho & Jeffrey L. Platt

  4. Transplantation Biology and the Department of Surgery, Mayo Clinic, 200 First Street SW, Medical Sciences 2-66, Rochester, 55905, Minnesota, USA

    Marilia Cascalho & Jeffrey L. Platt

Authors
  1. Brenda M. Ogle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marilia Cascalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeffrey L. Platt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey L. Platt.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Related links

Related links

DATABASES

Entrez Gene

ADAM1

ADAM2

ADAM12

Fah

Izumo

FURTHER INFORMATION

Jeffrey Platt's laboratory

Glossary

DIFFERENTIATION

The acquisition of 'mature' cellular characteristics, which can be connected with the acquisition of the cell's mature function. Differentiation can be terminal, which means that the cell adopts a different set of characteristics and will not proliferate.

HETEROKARYON

A cell formed by the fusion of two or more cells of different types and having two or more distinct nuclei.

SYNKARYON

A cell formed by the fusion of two or more cells and having one common nucleus, formed by nuclear fusion.

HYBRID CELL

A cell that arises from the fusion of two different cells.

STALK

A structure that is formed when a fusion protein from one cell interacts with a receptor on a neighbouring cell, and the attractive force exceeds the repulsive force caused by hydration.

PORE

A structure that is formed on completion of the fusion of cell membranes; the 'stalk' elongates to form a fusion pore.

FUSOGEN

A protein or molecule that directly mediates the merging of cell membranes (for example, polyethylene glycol and calcium).

OSTEOCLAST

A bone-tissue-resorbing cell that is formed by the fusion of mononuclear cell precursors to yield multinucleated cells. Osteoclasts contribute to bone development and homeostasis, including the formation of canals and cavities.

ADAM FAMILY

A group of transmembrane proteins that contains a disintegrin and metalloprotease domain. Proteins of the ADAM family can promote cell adhesion and/or catalyse proteolysis and might promote or enable cells to fuse.

PLOIDY

The number of single sets of chromosomes in a cell.

TROPHOBLAST

A cell from the outermost layer of cells of the blastocyst, constituting the interface between the foetus and the mother. Cells of the trophoblast (cytotrophoblast) ultimately fuse to form the syncytiotrophoblast of the placenta.

SYNCYTIUM

A cell containing two or more nuclei, usually having a large, continuous mass of cytoplasm. A syncytium is generally formed by fusion of two or more cells of the same type.

MATERNAL-FETAL BARRIER

The placenta allows the exchange of oxygen and nutrients but restricts the interchange of cells between the foetus and the mother's uterus.

TRANSDIFFERENTIATION

A change from one differentiated state of a cell to another. Transdifferentiation is thought to be rare and possibly limited to stem cells.

FISH

Fluorescence in situ hybridization. A technique in which one or more genes are located in chromosomes by hybridization of fluorescently labelled complementary DNA. FISH can be used to determine the number of copies of a specific sequence of DNA in a cell.

HAEMATOPOIETIC

Related to the blood or blood cells. Haematopoietic stem cells give rise to cells of the various lineages of the blood and have been found to fuse with cells from non-haematopoietic tissues.

PARENCHYMAL CELL

A cell that contributes to the essential structure and/or function of an organ, in contrast to stroma or blood vessels.

MYOTUBE

A developing fibre of skeletal muscle with a tubular appearance.

HEPATOCYTE

A parenchymal cell of the liver. Hepatocytes are the only cells in mature humans that can undergo mitosis without cytokinesis to form multinucleated cell masses.

MYELOMONOCYTIC CELL

An immature white blood cell of the granulocyte–monocyte–histiocyte lineage. These cells typically have cytoplasmic granules, a large horse-shoe-shaped nucleus and cell markers characteristic of immature myeloid cells. The term can refer to leukaemia cells exhibiting both myeloid and monocytic properties.

PORCINE ENDOGENOUS RETROVIRUS

A retrovirus in germline DNA that is dormant in normal pigs and exists as DNA copies in every cell.

ALLOPHENIC MICE

Tetraparental mice formed by the aggregation of blastocyst cells or cells from early embryos of two genetically pure lines of mice. The cell aggregates are implanted in the uterus of a foster mother.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ogle, B., Cascalho, M. & Platt, J. Biological implications of cell fusion. Nat Rev Mol Cell Biol 6, 567–575 (2005). https://doi.org/10.1038/nrm1678

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm1678

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing