Recent studies have demonstrated that transplanted bone marrow cells can turn into unexpected lineages including myocytes, hepatocytes, neurons and many others1. A potential problem, however, is that reports discussing such ‘transdifferentiation’ in vivo tend to conclude donor origin of transdifferentiated cells on the basis of the existence of donor-specific genes such as Y-chromosome markers1. Here we demonstrate that mouse bone marrow cells can fuse spontaneously with embryonic stem cells in culture in vitro that contains interleukin-3. Moreover, spontaneously fused bone marrow cells can subsequently adopt the phenotype of the recipient cells, which, without detailed genetic analysis, might be interpreted as ‘dedifferentiation’ or transdifferentiation.
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Weissman, I. L. Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 287, 1442–1446 (2000)
Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J. & Campbell, K. H. Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810–813 (1997)
Clarke, D. L. et al. Generalized potential of adult neural stem cells. Science 288, 1660–1663 (2000)
Pittenger, M. F. et al. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143–147 (1998)
Ferrari, G. et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279, 1528–1530 (1998)
Petersen, B. E. et al. Bone marrow as a potential source of hepatic oval cells. Science 284, 1168–1170 (1999)
Theise, N. D. et al. Liver from bone marrow in human. Hepatology 32, 11–16 (2000)
Lagasse, E. et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nature Med. 6, 1229–1234 (2000)
Brazelton, T. R., Rossi, F. M. V., Keshet, G. I. & Blau, H. M. From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290, 1775–1779 (2000)
Mezey, E., Chandross, K. J., Harta, G., Maki, R. A. & McKercher, S. R. Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290, 1779–1782 (2000)
Krause, D. S. et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105, 369–377 (2001)
Hadjantonakis, A. K., Gertsenstein, M., Ikawa, M., Okabe, M. & Nagy, A. Generating green fluorescent mice by germline transmission of green fluorescent ES cells. Mech. Dev. 76, 79–90 (1998)
Kawasome, H. et al. Targeted disruption of p70s6k defines its role in protein synthesis and rapamycin sensitivity. Proc. Natl Acad. Sci. USA 95, 5033–5038 (1998)
Minamino, T. et al. MEKK1 suppresses oxidative stress-induced apoptosis of embryonic stem cell-derived cardiac myocytes. Proc. Natl Acad. Sci. USA 96, 15127–15132 (1999)
Hamazaki, T. et al. Hepatic maturation in differentiating embryonic stem cells in vitro. FEBS Lett. 497, 15–19 (2001)
Nichols, J. et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transciption factor Oct4. Cell 95, 379–391 (1998)
Nishimoto, M., Fukushima, A., Okuda, A. & Muramatsu, M. The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2. Mol. Cell. Biol. 19, 5453–5465 (1999)
Kawasaki, H. et al. Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28, 31–40 (2000)
Everett, C. A. & West, J. D. The influence of ploidy on the distribution of cells in chimaeric mouse blastocysts. Zygote 4, 59–66 (1996)
Tada, M., Takahama, Y., Abe, K., Nakatsuji, N. & Tada, T. Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells. Curr. Biol. 11, 1553–1558 (2001)
Tada, M., Tada, T., Lefebvre, L., Barton, S. C. & Syrani, M. A. Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells. EMBO J. 16, 6510–6520 (1997)
Parwaresch, M. R., Kreipe, H. & Radzun, H. J. Human macrophage hybrid forming spontaneous giant cells. Virchows Arch. B 51, 89–96 (1986)
Chiozzi, P. et al. Spontaneous cell fusion in macrophage cultures expressing high levels of the P2Z/P2X7 receptor. J. Cell Biol. 138, 697–706 (1997)
Falzoni, S. et al. The purinergic P2Z receptor of human macrophage cells. Characterization and possible physiological role. J. Clin. Invest. 95, 1207–1216 (1995)
Enelow, R. I., Sullivan, G. W., Carper, H. T. & Mandell, G. L. Induction of multinucleated giant cell formation from in vitro culture of human monocytes with interleukin-3 and interferon-β: comparison with other stimulating factors. Am. J. Resp. Cell Mol. Biol. 6, 57–62 (1992)
The authors are indebted to A. Nagy for providing embryonic stem cell lines; Y. Yoneda for discussion; J. Crawford, D. Steindler, S. May and S. Sugrue for critical reading of the manuscript; and G. Brown, M. Jorgenson, A. Meacham, N. Devine, and Diagnostic Cytogenetics for technical assistance. This work was supported by grants from the National Institutes of Health (to N.T. and E.W.S.).
The authors declare that they have no competing financial interests
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Terada, N., Hamazaki, T., Oka, M. et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416, 542–545 (2002). https://doi.org/10.1038/nature730
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