Skip to main content
SpringerLink
Log in

Cell fusion and plasticity

  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

Cell plasticity is a central issue in stem cell biology. In many recent discussions, observation of cell fusion has been seen as a confounding factor which calls into question published results concerning cell plasticity of, particularly, adult stem cells. An examination of the voluminous literature of "somatic cell fusion" suggests the relatively frequent occurrence of "spontaneous" cell fusion and shows that the complicated cellular phenotypes which it can give rise to have long been recognized. Here, a brief overview of this field is presented, with emphasis on studies of special relevance to current work on cell plasticity.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baron MH & Maniatis T (1986) Rapid reprogramming of globin gene expression in transient heterokaryons. Cell 46: 591–562.

    Article  PubMed  CAS  Google Scholar 

  • Barski G, Sorieul S & Cornefert F (1961) 'Hybrid' type cells in combined cultures of two different mammalian cell strains. J Natl Cancer Inst 26: 1269–1291.

    PubMed  CAS  Google Scholar 

  • Barski G & Cornefert F (1962) Characteristics of 'hybrid'-type clonal cell lines obtained from mixed cultures in vitro. J Natl Cancer Inst 28: 801–821.

    PubMed  CAS  Google Scholar 

  • Bengtsson BO, Nabholz M, Kennett R, Bodmer WF, Povey S & Swallow D (1975) Human intraspecific somatic cell hybrids: A genetic and karyotypic analysis of crosses between lymphocytes and D98/AH-2. Somatic Cell Genet 1: 41–64.

    Article  PubMed  CAS  Google Scholar 

  • Blau HM & Blakely BT (1999) Plasticity of cell fate: Insights from heterokaryons. Cell Develop Biol 10: 267–272.

    Article  CAS  Google Scholar 

  • Blau HM, Chiu CP & Webster C (1983) Cytoplasmic activation of human nuclear genes in stable heterokaryons. Cell 32: 1171–1180.

    Article  PubMed  CAS  Google Scholar 

  • Blau HM, Parlath GK, Hardeman EC, Chin CP, Silberstein L, Webster SG, Miller SC & Webster C (1985) Plasticity of the differentiated state. Science 230: 758–766.

    PubMed  CAS  Google Scholar 

  • Brazelton TR, Rossi FMV, Keshet GI & Blau HM (2000) From marrow to brain: Expression of neuronal phenotypes in adult mice. Science 290: 1775–1779.

    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: 455–457.

    Article  PubMed  CAS  Google Scholar 

  • Briggs R & King TJ (1960) Nuclear transplantation studies on the early gastrula (Rana pipiens). Devel Biol 2: 252–270.

    Article  CAS  Google Scholar 

  • Bruno J, Reich NR & Lucas JJ (1981) Globin synthesis in hybrid cells constructed by transplantation of dormant avian erythrocyte nuclei into enucleated fibroblasts. Mol Cell Biol 1: 1163–1176.

    PubMed  CAS  Google Scholar 

  • Bunn CL, Wallace DC and Eisenstadt JM (1974) Cytoplasmic inheritance of chloramphenicol resistance in mouse tissue cells. Proc Natl Acad Sci USA 71: 1681–1685.

    Article  PubMed  CAS  Google Scholar 

  • Carter SB (1967) Effects of cytochalasen on mammalian cells. Nature 213: 261–266.

    Article  PubMed  CAS  Google Scholar 

  • Choi J, Costa ML, Mermelstein CS, Chagas C, Holtzer S & Holtzer H (1990) MyoD converts primary dermal fibroblasts, chondroblasts, smooth muscle, and retinal pigmented epithelial cells into striated mononucleated myoblsts and multinucleated myotubes. Proc Natl Acad Sci USA 87: 7988–7992.

    Article  PubMed  CAS  Google Scholar 

  • Davidson RL & Ephrussi B (1965) A selective system for the isolation of hybrids between L cells and normal cells. Nature 205: 1170–1171.

    Article  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 

  • Davidson RL, Ephrussi B & Yamamoto K (1968) Regulation of melanin synthesis in mammalian cells, as studied by somatic hybridization. I. Evidence for negative control. J Cell Physiol 72: 115–127.

    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 

  • Eglitis MA & Mezey E (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci USA 94: 4080–4085.

    Article  PubMed  CAS  Google Scholar 

  • Engel E, McGee BJ & Harris H (1969) Cytogenettic and nuclear studies on A9 and B82 cells fused together by Sendai virus: The early phase. J Cell Sci 5: 93–120.

    PubMed  CAS  Google Scholar 

  • Ferrari G, Cusella-DeAngelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G & Mavilio F (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279: 1528–1530.

    Article  PubMed  CAS  Google Scholar 

  • Finch BW & Ephrussi B (1967) Retention of multiple developmental potentialities by cells of a mouse testicular teratocarcinoma during prolonged culture in vitro and their extinction upon hybridization with cells of permanent lines. Proc Natl Acad Sci USA 57: 615–621.

    Article  PubMed  Google Scholar 

  • Fischberg M, Gurdon JB & Elsdale TR (1958) Nuclear transplantation in Xenopus laevis. Nature 181: 424.

    Article  Google Scholar 

  • Fougere C & Weiss MC (1978) Phenotypic exclusion in mouse melanoma-rat hepatoma cells: Pigment and albumin production are not reexpressed simultaneously. Cell 15: 843–854.

    Article  PubMed  CAS  Google Scholar 

  • Gopalakrisnan TV & Anderson WF (1979) Epigenetic activtion of phenylalanine hydroxylase in mouse erythroleukemia cells by the cytoplast of rat hepatoma cells. Proc Natl Acad Sci USA 76: 3932–3936.

    Article  Google Scholar 

  • Gurdon JB (1962) Adult frogs derived from the nuclei of single somatic cells. Develop Biol 4: 256–273.

    Article  PubMed  CAS  Google Scholar 

  • Gurdon JB & Melton DA (1981) Gene transfer in amphibian eggs and oocytes. Ann Rev Genet 15: 189–218.

    Article  PubMed  CAS  Google Scholar 

  • Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, Kunkel LM & Mulligan RC (1999) Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401: 390–394.

    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 

  • Hernandez LD, Hoffman LR & White JM (1996) Virus-cell and cell-cell fusion. Annu Rev Cell Dev Biol 12: 627–661.

    Article  PubMed  CAS  Google Scholar 

  • Iwakura Y, Nozaki M, Asano M, Yoshida MC, Tsukada Y, Hibi N, Ochiai A, Tahara E, Tosu M & Sekiguchi T (1985) Pleiotropic phenotypic expression in cybrids derived from mouse teratocarcinoma cells fused with rat myoblasts. Cell 43: 771–779.

    Article  Google Scholar 

  • Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK & Goodell MA (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107: 1395–1402.

    Article  PubMed  CAS  Google Scholar 

  • Jami J, Failly C & Ritz E (1973) Lack of expression of differentiation in mouse teratoma-fibroblast somatic cell hybrids. Exp Cell Res 76: 191–199.

    Article  PubMed  CAS  Google Scholar 

  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, & Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418: 41–9.

    Article  PubMed  CAS  Google Scholar 

  • Kahn CR, Berttolotti R, Ninio M & Weiss MC (1981a) Short-lived cytoplasmic regulators of gene expression in cell hybrids. Nature 290: 717–720.

    Article  PubMed  CAS  Google Scholar 

  • Kahn CR, Gopalakrishnan TV & Weiss MC (1981b) Transfer of heritable properties by cell cybridization: Specificity and the role of selective pressure. Somatic Cell Genet 7: 547–565.

    Article  PubMed  CAS  Google Scholar 

  • Korbling M, Katz RL, Khanna A, Ruifrok AC, Rondon G, Albitar M, Champlin RE & Estrov Z (2002) Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. N Engl J Med 346: 738–746.

    Article  PubMed  Google Scholar 

  • Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S & Sharkis SJ (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105: 369–377.

    Article  PubMed  CAS  Google Scholar 

  • Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL & Grompe M (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nature Med 6: 1229–1234.

    Article  PubMed  CAS  Google Scholar 

  • Lemiscka I (2002) Rethinking somatic stem cell plasticity (Commentary). Nature Biotechnol 20: 425.

    Article  CAS  Google Scholar 

  • Lewis WH (1927) The formation of giant cells in tissue culture and their similarity to those in tuberculous lesions. Am Rev Tuberc 15: 616–628.

    Google Scholar 

  • Lipsich LA, Kates JR & Lucas JJ (1979) Expression of a liverspecific function by mouse fibroblast nuclei transplanted into rat hepatoma cytoplasts. Nature 281: 74–76.

    Google Scholar 

  • Lipsich LA, Lucas JJ & Kates JR (1978) Cell cycle dependence of the reactivation of chick erythrocyte nuclei after transplantation into mouse L929 cytoplasts. J Cell Physiol 97: 199–208.

    Article  PubMed  CAS  Google Scholar 

  • Littlefield JW (1964) Selection of hybrids from matings of fibroblasts in vitro and their presumed recombinants. Science 145: 709–710.

    PubMed  CAS  Google Scholar 

  • Lucas JJ (1983) Somatic cell hybridization. In: N Maclean, SP Gregory & RA Flavell (eds.) Eukaryotic Genes: Their Structure, Activity and Regulation (pp. 117-126) Butterworths, London.

  • Lucas JJ & Kates JR (1976) The construction of viable nuclearcytoplasmic hybrid cells by nuclear transplantation. Cell 7: 397–405.

    Article  PubMed  CAS  Google Scholar 

  • Maclean N & Hall BK (1987) Cell Commitment and Differentiation. Cambridge University Press, Cambridge.

    Google Scholar 

  • McBurney MW (1977) Hemoglobin synthesis in cell hybrids formed between teratocarcinoma cells and friend erythroleukemia cells. Cell 12: 653–662.

    Article  PubMed  CAS  Google Scholar 

  • McBurney MW, Featherstone MS & Kaplan H (1978) Activation of teratocarcinoma-derived hemoglobin genes in teratocarcinomafriend cell hybrids. Cell 15: 1323–1330.

    Article  PubMed  CAS  Google Scholar 

  • McBurney MW & Strutt B (1979) Fusion of embryonal carcinoma cells to fibroblast cells, cytoplasts, and karyoplasts. Exp Cell Res 124: 171–180.

    Article  PubMed  CAS  Google Scholar 

  • McKay R (2002) A more astonishing hypothesis (Commentary). Nature Biotechnol 20: 426–427.

    Article  CAS  Google Scholar 

  • Mercer WE & Schlegel RA (1982) Cytoplasts can transfer factor(s) that stimulate quiescent fibroblasts to enter S phase. J Cell Physiol 110: 311–314.

    Article  PubMed  CAS  Google Scholar 

  • Mevel-Ninio M & Weiss MC (1981) Immunofluorescence analysis of the time-course of extinction, reexpression, and activation of albumin production in rat hepatoma-mouse fibroblast heterokaryons and hybrids. J Cell Biol 90: 339–350.

    Article  PubMed  CAS  Google Scholar 

  • Mezey E, Chandross KJ, Harta G, Maki RA & McKercher SR (2000) Turning blood into brain cells bearing neuronal antigens generated in vivo from bone marrow. Science 290: 1779–1782.

    Article  PubMed  CAS  Google Scholar 

  • Migeon BR & Miller CS (1968) Human-mouse somatic cell hybrids with single human chromosome (group E): Link with thymidine kinase activity. Science 162: 1005–1006.

    PubMed  CAS  Google Scholar 

  • Miller RA & Ruddle FH (1976) Pluripotent teratocarcinomathymocyte somatic cell hybrids. Cell 9: 45–55.

    Article  PubMed  CAS  Google Scholar 

  • Okada Y (1958) The fusion of Ehrlich's tumor cells caused by HVJ virus in vitro. Biken's J 1: 103–110.

    Google Scholar 

  • Okada Y & Murayama F (1965) Multinucleated giant cell formation by fusion between cells of two different strains. Exp Cell Res 40: 154–158.

    Article  PubMed  CAS  Google Scholar 

  • Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A & Anversa P (2001) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Nat. Acad Sci USA 98: 10344–10349.

    Article  PubMed  CAS  Google Scholar 

  • PesceM, Gross MK & Scholer HR (1998) In line with our ancestors: Oct-4 and the mammalian germ. Bioessays 20: 722–732.

    Article  PubMed  CAS  Google Scholar 

  • Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS & Goff JP (1999) Bone marrow as a potential source of hepatic oval cells. Science 284: 1168–1170.

    Article  PubMed  CAS  Google Scholar 

  • Pontecorvo G (1976) Production of indefinitly multiplying mammalian somatic cell hybrids by polyethylene glycol (PEG) treatment. Somatic Cell Genet 1: 397–400.

    Article  Google Scholar 

  • Poste G & Reeve P (1971) Formation of hybrid cells and heterokaryons by fusion of enucleated and nucleated cells. Nature, New Biol 229: 123–125.

    Article  CAS  Google Scholar 

  • Poste G & Reeve P (1972) Enucleation of mammalian cells by cytochalasin B. II. Formation of hybrid cells and heterokaryons by fusion of anucleate and enucleated cells. Exp Cell Res 73: 287–294.

    Article  PubMed  CAS  Google Scholar 

  • Prescott DM, Meyerson D & Wallace J (1972) Enucleation of mammalian cells with cytochalasin B. Exp Cell Res 71: 480–485.

    Article  PubMed  CAS  Google Scholar 

  • Rao P & Johnson RT (1970) Mammalian cell fusion: Studies on the regulation of DNA synthesis and mitosis. Nature 225: 159–164.

    Article  PubMed  CAS  Google Scholar 

  • Resnitzky DM, Gossen M, Bujard H & Reed SI (1994) Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system. Mol Cell Biol 14: 1669–1679.

    PubMed  CAS  Google Scholar 

  • Ringertz NR & Savage RE (1976) Cell Hybrids. Academic Press, New York.

    Google Scholar 

  • Ruddle FH, Chapman VM, Ricciuti F, Murnane M, Klebe R & Meera Khan P (1971) Linkage relationships of seventeen human gene loci as determined by man-mouse somatic cell hybrids. Nature, New Biol 232: 69–73.

    CAS  Google Scholar 

  • Ruddle FH & Kucherlapati RS (1974) Hybrid cells and human genes. Sci Am 231: 36–44.

    Article  PubMed  CAS  Google Scholar 

  • Russo S, Tomatis D, Collo G, Tarone G & Tato F (1998) Myogenic conversion of NIH3T3 cells by exogenous MyoD family members: Dissociation of terminal differentiation from myotube formation. J Cell Sci 111: 691–700.

    PubMed  CAS  Google Scholar 

  • Sata M, Saiura A, Kunisato A, Tojo A, Okada S, Tokuhisa T, Hirai H, Makuuchi M, Hirata Y & Nagai R (2002) Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nature Med 8: 403–409.

    Article  PubMed  CAS  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 

  • Shimizu K, Sugiyama S, Aikawa M, Fukumoto Y, Rabkin E, Libby P & Mitchell RN (2001) Host bone-marrow cells are a source of donor intimal smooth-muscle-like cells in murine aortic transplant arteriopathy. Nature Med 7: 738–741.

    Article  PubMed  CAS  Google Scholar 

  • Spear BT & Tilghman SM (1990) Role of alpha-fetoprotein regulatory elements in transcriptional activation in transient heterokaryons. Mol Cell Biol 10: 5047–5054.

    PubMed  CAS  Google Scholar 

  • Surani MA (2001) Reprogramming of genome function through epigenetic inheritance. Nature 414: 122–128.

    Article  PubMed  CAS  Google Scholar 

  • Szybalski W, Szbalski EH & Ragni G (1962) Genetic studies with human cell lines. Natl Cancer Inst Monograph 7: 75–89.

    Google Scholar 

  • Tada M, Tada T, Lefebvre L, Barton SC & Surani MA (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, Nakatsuji N & Tada T (2001) Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr Bio 11: 1553–1558.

    Article  CAS  Google Scholar 

  • Takagi N, Yoshida MA, Sugawara O & Sasaki M (1983) Reversal of X-inactivation in female mouse somatic cells hybridized with murine teratocarcinoma cells in vitro. Cell 34: 1053–1062.

    Article  PubMed  CAS  Google Scholar 

  • Taylor MV (2002) Muscle differentiation: How two cells become one. Curr Biol 12: R224–R228.

    Article  PubMed  CAS  Google Scholar 

  • Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE & Scott EW (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous fusion. Nature 416: 542–545.

    Article  PubMed  CAS  Google Scholar 

  • Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O & Krause DS (2000) Liver from bone marrow in human. Hepatology 32: 11–16.

    Article  PubMed  CAS  Google Scholar 

  • Tsai YL, Kittappa R & McKay RDG (2002) Plasticity, niches, and the use of stem cells (Meeting review). Develop Cell 2: 707–712.

    Article  CAS  Google Scholar 

  • Veomett G, Prescott DM, Shay J & Porter KR (1974) Reconstruction of mammalian cells from nuclear and cytoplasmic components separated by treatment with cytochalasin B. Proc Natl Acad Sci USA 71: 1999–2002.

    Article  PubMed  CAS  Google Scholar 

  • Vignery A (2000) Osteoclasts and giant cells: Macrophagemacrophage fusion mechanisms. Intnatl J Exptl Path 81: 291–304.

    Article  CAS  Google Scholar 

  • Weiss MC & Green H (1967) Human-mouse hybrid cell lines containing partial compements of human chromosomes and functioning human genes. Proc Natl Acad Sci USA 58: 1104–1111.

    Article  PubMed  CAS  Google Scholar 

  • Weissman IL, Anderson DJ & Gage F (2001) Stem and progenitor cells: Origins, phenotypes, lineage commitments, and transdifferentiation. Annu Rev Cell Dev Biol 17: 387–403.

    Article  PubMed  CAS  Google Scholar 

  • White JM & Rose MD (2001) Yeast mating: Getting close to membrane merger. Curr Biol 11: R16–R20.

    Article  PubMed  CAS  Google Scholar 

  • Wilmut I, Beaujean N, de Sousa PA, Dinnyes A, King TJ, Paterson LA, Wells DN & Young LE (2002) Somatic cll nuclear transfer. Nature 419: 583–586.

    Article  PubMed  CAS  Google Scholar 

  • Wimmel A, Lucibello FC, Sewing A, Adolf S & Muller R (1994) Inducible acceleration of G1 progression through tetercyclineregulated expression of human cyclin E. Oncogene 9: 995–997.

    PubMed  CAS  Google Scholar 

  • Wright WE & Hayflick L (1972) Formation of anucleate and multinucleate cells in normal and SV40 transformed WI-38 by cytochalasin B. Exp Cell Res 74: 187–194.

    Article  PubMed  CAS  Google Scholar 

  • Wu KJ, Samuelson LC, Howard G, Meisler MH & Darlington GJ (1991) Transactivation of pancreas-specific gene sequences in somatic cell hybrids. Mol Cell Biol 11: 4423–4430.

    PubMed  CAS  Google Scholar 

  • Yeom YI, Fuhrmann G, Ovitt CE, Brehm A, Ohbo K, Gross M, Hubner K & Scholer HR (1996) Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells. Develop 122: 881–894.

    CAS  Google Scholar 

  • Ying QL, Nichols J, Evans EP & Smith AG (2002) Changing potency by spontaneous fusion. Nature 416: 545–548.

    Article  PubMed  CAS  Google Scholar 

  • Zepp HD, Conover JH, Hirschhorn K & Hodes HL (1971) Human mosquito somatic cell hybrids induced by ultraviolet-inactivated Sendai virus. Nature, New Biol 229: 119–121.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO, U.S.A

    Joseph J. Lucas

  2. Department of Pathology, University of Florida College of Medicine, Gainesville, FL, U.S.A. (Author for correspondence; E-mail

    Naohiro Terada

Authors
  1. Joseph J. Lucas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naohiro Terada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Naohiro Terada.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lucas, J.J., Terada, N. Cell fusion and plasticity. Cytotechnology 41, 103–109 (2003). https://doi.org/10.1023/A:1024870605447

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1024870605447

Search

Navigation