Science

Rethinking nomenclature for interspecies cell fusions


  • 1.

    Ephrussi, B. & Weiss, M. C. Interspecific hybridization of somatic cells. Proc. Natl Acad. Sci. USA 53, 1040–1042 (1965).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 2.

    Harris, H., Watkins, J. F., Campbell, G. L., Evans, E. P. & Ford, C. E. Mitosis in hybrid cells derived from mouse and man. Nature 207, 606–608 (1965).

    CAS 
    PubMed 

    Google Scholar
     

  • 3.

    Hyun, I. et al. Ethical standards for human-to-animal chimera experiments in stem cell research. Cell Stem Cell 1, 159–163 (2007).

    PubMed 

    Google Scholar
     

  • 4.

    Greely, H. T., Cho, M. K., Hogle, L. F. & Satz, D. M. Thinking about the human neuron mouse. Am. J. Bioeth. 7, 27–40 (2007).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 5.

    Matthews, K. R. W., Wagner, D. S. & Warmflash, A. Stem cell-based models of embryos: the need for improved naming conventions. Stem Cell Rep. 16, 1014–1020 (2021).


    Google Scholar
     

  • 6.

    National Academies of Sciences, Engineering, and Medicine; Policy and Global Affairs; Committee on Science, Technology, and Law; and Committee on Ethical, Legal, and Regulatory Issues Associated with Neural Chimeras and Organoids. The Emerging Field of Human Neural Organoids, Transplants, and Chimeras: Science, Ethics, and Governance (National Academies Press, 2021). These guidelines carefully consider stem cell biology approaches that risk blurring species boundaries.

  • 7.

    Robert, J. S. & Baylis, F. Crossing species boundaries. Am. J. Bioeth. 3, 1–13 (2003).

    PubMed 

    Google Scholar
     

  • 8.

    Barski, G., Sorieul, S. & Cornefert, F. Production of cells of a “hybrid” nature in culturs in vitro of 2 cellular strains in combination [French]. C. R. Hebd. Seances Acad. Sci. 251, 1825–1827 (1960).

    CAS 
    PubMed 

    Google Scholar
     

  • 9.

    Creagan, R. P. & Ruddle, F. H. The clone panel: a systematic approach to gene mapping using interspecific somatic cell hybrids. Cytogenet. Cell Genet. 14, 282–286 (1975).

    CAS 
    PubMed 

    Google Scholar
     

  • 10.

    Nabholz, M., Miggiano, V. & Bodmer, W. Genetic analysis with human–mouse somatic cell hybrids. Nature 223, 358–363 (1969).

    CAS 
    PubMed 

    Google Scholar
     

  • 11.

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

    PubMed 

    Google Scholar
     

  • 12.

    Parray, H. A. et al. Hybridoma technology a versatile method for isolation of monoclonal antibodies, its applicability across species, limitations, advancement and future perspectives. Int. Immunopharmacol. 85, 106639 (2020).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 13.

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

    CAS 
    PubMed 

    Google Scholar
     

  • 14.

    Baron, M. H. & Maniatis, T. Rapid reprogramming of globin gene expression in transient heterokaryons. Cell 46, 591–602 (1986).

    CAS 
    PubMed 

    Google Scholar
     

  • 15.

    Piccolo, F. M. et al. Using heterokaryons to understand pluripotency and reprogramming. Philos. Trans. R. Soc. Lond. B Biol. Sci. 366, 2260–2265 (2011).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 16.

    Cowan, C. A., Atienza, J., Melton, D. A. & Eggan, K. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309, 1369–1373 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • 17.

    Lee, J. H. et al. Systematic identification of cis-silenced genes by trans complementation. Hum. Mol. Genet. 18, 835–846 (2009).

    CAS 
    PubMed 

    Google Scholar
     

  • 18.

    Looney, T. J. et al. Systematic mapping of occluded genes by cell fusion reveals prevalence and stability of cis-mediated silencing in somatic cells. Genome Res. 24, 267–280 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 19.

    Cáceres, J. F., Screaton, G. R. & Krainer, A. R. A specific subset of SR proteins shuttles continuously between the nucleus and the cytoplasm. Genes Dev. 12, 55–66 (1998).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 20.

    Piñol-Roma, S. & Dreyfuss, G. Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature 355, 730–732 (1992).

    PubMed 

    Google Scholar
     

  • 21.

    Ohnuki, M. & Takahashi, K. Present and future challenges of induced pluripotent stem cells. Philos. Trans. R. Soc. Lond. B Biol. Sci. 370, 20140367 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 22.

    National Research Council; Division on Earth and Life Studies; Board on Life Sciences; Policy and Global Affairs; and Committee on Science, Engineering, and Public Policy. Scientific and Medical Aspects of Human Reproductive Cloning (National Academies Press, 2002).

  • 23.

    NIH. NIH research involving introduction of human pluripotent cells into non-human vertebrate anima0l pre-gastrulation embryos: notice number NOT-OD-15-158. National Institutes of Health https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-158.html (2015).

  • 24.

    Zhao, X.-Y. et al. iPS cells produce viable mice through tetraploid complementation. Nature 461, 86–90 (2009).

    CAS 
    PubMed 

    Google Scholar
     

  • 25.

    Boland, M. J. et al. Adult mice generated from induced pluripotent stem cells. Nature 461, 91–94 (2009).

    CAS 
    PubMed 

    Google Scholar
     

  • 26.

    Kang, L., Wang, J., Zhang, Y., Kou, Z. & Gao, S. iPS cells can support full-term development of tetraploid blastocyst-complemented embryos. Cell Stem Cell 5, 135–138 (2009).

    CAS 
    PubMed 

    Google Scholar
     

  • 27.

    Gafni, O. et al. Derivation of novel human ground state naive pluripotent stem cells. Nature 504, 282–286 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • 28.

    Wu, J. et al. Interspecies chimerism with mammalian pluripotent stem cells. Cell 168, 473–486.e15 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 29.

    Tan, T. et al. Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo. Cell 184, 2020–2032.e14 (2021). This study demonstrates the potential of human pluripotent stem cells to contribute to organismal development in appreciable numbers.

    CAS 
    PubMed 

    Google Scholar
     

  • 30.

    Aach, J., Lunshof, J., Iyer, E. & Church, G. M. Correction: Addressing the ethical issues raised by synthetic human entities with embryo-like features. eLife 6, e27642 (2017).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 31.

    Warmflash, A., Sorre, B., Etoc, F., Siggia, E. D. & Brivanlou, A. H. A method to recapitulate early embryonic spatial patterning in human embryonic stem cells. Nat. Methods 11, 847–854 (2014).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 32.

    van den Brink, S. C. et al. Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells. Development 141, 4231–4242 (2014).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 33.

    Lovell-Badge, R. et al. ISSCR guidelines for stem cell research and clinical translation: the 2021 update. Stem Cell Rep. 16, 1398–1408 (2021).


    Google Scholar
     

  • 34.

    McNamee, S. Human–animal hybrids and chimeras: what’s in a name? Eur. J. Bioeth. 6, 45–66 (2015). These guidelines define categories of research and oversight levels required for human stem cell research, including the need for a compelling scientific rationale for experiments involving chimeric organisms.


    Google Scholar
     

  • 35.

    St John, J. & Lovell-Badge, R. Human–animal cytoplasmic hybrid embryos, mitochondria, and an energetic debate. Nat. Cell Biol. 9, 988–992 (2007). This essay explores public communication and opinion about human–animal cybrid, hybrid and chimera experiments, and examines the connection between that reporting and research policy, particularly in the United Kingdom.


    Google Scholar
     

  • 36.

    Li, X. et al. Generation and application of mouse-rat allodiploid embryonic stem cells. Cell 164, 279–292 (2016).

    CAS 
    PubMed 

    Google Scholar
     

  • 37.

    Gokhman, D. et al. Human–chimpanzee fused cells reveal cis-regulatory divergence underlying skeletal evolution. Nat. Genet. 53, 467–476 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 38.

    Agoglia, R. M. et al. Primate cell fusion disentangles gene regulatory divergence in neurodevelopment. Nature 592, 421–427 (2021). Together with Gokhman et al., this report extends cell fusions to human and chimpanzee pluripotent stem cells and highlights the need for a revised nomenclature.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 39.

    Song, J. H. T. et al. Genetic studies of human–chimpanzee divergence using stem cell fusions. Proc. Natl Acad. Sci. USA 118, e2117557118 (2021).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 40.

    Department of Health. Human Fertilisation and Embryology Act 2008: explanatory notes. Legislation.gov.uk https://www.legislation.gov.uk/ukpga/2008/22/notes (2008).

  • 41.

    Matthews, K. R. & Moralí, D. National human embryo and embryoid research policies: a survey of 22 top research-intensive countries. Regen. Med. 15, 1905–1917 (2020).

    CAS 
    PubMed 

    Google Scholar
     

  • 42.

    Brownback, S. S.659 — Human Chimera Prohibition Act of 2005. Congress.gov https://www.congress.gov/109/bills/s659/BILLS-109s659is.pdf (2005).

  • 43.

    Smith, C. H.R.3542 — Human-Animal Chimera Prohibition Act of 2021. Congress.gov https://www.congress.gov/bill/117th-congress/house-bill/3542 (2021).

  • 44.

    Hyun, I., Bredenoord, A. L., Briscoe, J., Klipstein, S. & Tan, T. Human embryo research beyond the primitive streak. Science 371, 998–1000 (2021).

    CAS 
    PubMed 

    Google Scholar
     

  • 45.

    Svoboda, E. The next frontier for human embryo research. Nature 597, S15–S17 (2021).

    CAS 

    Google Scholar
     

  • 46.

    Gallego Romero, I. et al. A panel of induced pluripotent stem cells from chimpanzees: a resource for comparative functional genomics. eLife 4, e07103 (2015). This report establishes a widely used panel of human and chimpanzee iPSCs enabling in vitro studies of recent evolutionary changes.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 47.

    Storchova, Z. & Kuffer, C. The consequences of tetraploidy and aneuploidy. J. Cell Sci. 121, 3859–3866 (2008).

    CAS 
    PubMed 

    Google Scholar
     

  • 48.

    Nagy, A. et al. Embryonic stem cells alone are able to support fetal development in the mouse. Development 110, 815–821 (1990).

    CAS 
    PubMed 

    Google Scholar
     

  • 49.

    Horii, T. et al. p53 suppresses tetraploid development in mice. Sci. Rep. 5, 8907 (2015).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 50.

    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).

    CAS 
    PubMed 

    Google Scholar
     

  • 51.

    Wilson, M. D. et al. Species-specific transcription in mice carrying human chromosome 21. Science 322, 434–438 (2008). This report establishes a framework for studying gene regulatory evolution using reproductive hybrids that has now been extended to composite cell lines.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 52.

    Kazuki, Y. et al. A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21. eLife 9, e56223 (2020).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • 53.

    Wittkopp, P. J., Haerum, B. K. & Clark, A. G. Evolutionary changes in cis and trans gene regulation. Nature 430, 85–88 (2004). This report describes a rare example of viable reproductive hybrids between chimpanzees and bonobos.

    CAS 
    PubMed 

    Google Scholar
     

  • 54.

    Hill, M. S., Vande Zande, P. & Wittkopp, P. J. Molecular and evolutionary processes generating variation in gene expression. Nat. Rev. Genet. 22, 203–215 (2021).

    CAS 
    PubMed 

    Google Scholar
     

  • 55.

    Vervaecke, H. & Van Elsacker, L. Hybrids between common chimpanzees (Pan troglodytes) and pygmy chimpanzees (Pan paniscus) in captivity. Mammalia 56, 667–669 (1992).


    Google Scholar
     

  • 56.

    Prado-Martinez, J. et al. Great ape genetic diversity and population history. Nature 499, 471–475 (2013).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 57.

    Greilhuber, J., Dolezel, J., Lysák, M. A. & Bennett, M. D. The origin, evolution and proposed stabilization of the terms “genome size” and “C-value” to describe nuclear DNA contents. Ann. Bot. 95, 255–260 (2005).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     



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