Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion

Abstract

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: GFP+ embryonic stem-like cells derived from mixed culture of GFP+ bone marrow cells and GFP embryonic stem cells.
Figure 2: Genetic analysis of BMESL cells.

References

  1. 1

    Weissman, I. L. Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 287, 1442–1446 (2000)

    ADS  CAS  Article  Google Scholar 

  2. 2

    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)

    ADS  CAS  Article  Google Scholar 

  3. 3

    Clarke, D. L. et al. Generalized potential of adult neural stem cells. Science 288, 1660–1663 (2000)

    ADS  CAS  Article  Google Scholar 

  4. 4

    Pittenger, M. F. et al. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143–147 (1998)

    ADS  Article  Google Scholar 

  5. 5

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

    ADS  CAS  Article  Google Scholar 

  6. 6

    Petersen, B. E. et al. Bone marrow as a potential source of hepatic oval cells. Science 284, 1168–1170 (1999)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Theise, N. D. et al. Liver from bone marrow in human. Hepatology 32, 11–16 (2000)

    CAS  Article  Google Scholar 

  8. 8

    Lagasse, E. et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nature Med. 6, 1229–1234 (2000)

    CAS  Article  Google Scholar 

  9. 9

    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)

    ADS  CAS  Article  Google Scholar 

  10. 10

    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)

    ADS  CAS  Article  Google Scholar 

  11. 11

    Krause, D. S. et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105, 369–377 (2001)

    CAS  Article  Google Scholar 

  12. 12

    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)

    CAS  Article  Google Scholar 

  13. 13

    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)

    ADS  CAS  Article  Google Scholar 

  14. 14

    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)

    ADS  CAS  Article  Google Scholar 

  15. 15

    Hamazaki, T. et al. Hepatic maturation in differentiating embryonic stem cells in vitro. FEBS Lett. 497, 15–19 (2001)

    CAS  Article  Google Scholar 

  16. 16

    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)

    CAS  Article  Google Scholar 

  17. 17

    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)

    CAS  Article  Google Scholar 

  18. 18

    Kawasaki, H. et al. Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28, 31–40 (2000)

    CAS  Article  Google Scholar 

  19. 19

    Everett, C. A. & West, J. D. The influence of ploidy on the distribution of cells in chimaeric mouse blastocysts. Zygote 4, 59–66 (1996)

    CAS  Article  Google Scholar 

  20. 20

    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)

    CAS  Article  Google Scholar 

  21. 21

    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)

    CAS  Article  Google Scholar 

  22. 22

    Parwaresch, M. R., Kreipe, H. & Radzun, H. J. Human macrophage hybrid forming spontaneous giant cells. Virchows Arch. B 51, 89–96 (1986)

    CAS  Article  Google Scholar 

  23. 23

    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)

    CAS  Article  Google Scholar 

  24. 24

    Falzoni, S. et al. The purinergic P2Z receptor of human macrophage cells. Characterization and possible physiological role. J. Clin. Invest. 95, 1207–1216 (1995)

    CAS  Article  Google Scholar 

  25. 25

    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)

    CAS  Article  Google Scholar 

Download references

Acknowledgements

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.).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Naohiro Terada.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Sign up for the Nature Briefing newsletter for a daily update on COVID-19 science.
Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing