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Reassessing the human mammary stem cell concept by modeling limiting dilution transplantation assays

Nature Medicine volume 15, pages 602–604 (2009)Cite this article

To the Editor:

In a recent study in Nature Medicine, Eirew et al.1 described a new protocol that can be used to accurately determine the frequency of human mammary stem cells (termed mammary repopulating units, MRUs) by limiting dilution transplantation assays (LDTAs). The authors presented five LDTAs showing the regeneration of colony-forming cells (CFCs) in xenografted gels seeded with varying numbers of input mammary cells. MRU frequency estimates were based on the standard single-hit Poisson model2 (SHPM). In the field of limiting dilution assays, this is the most parsimonious statistical model, which posits that a single cell (considered by Eirew et al.1 as a stem cell) is able to regenerate mammary structures containing multiple secondary CFCs. The SHPM is written as πi = exp (−fxi) , where πi is the expected proportion of negative xenografted gels (that is, free of CFCs), f is the frequency of MRUs and xi is the mammary cell input (cell dose), that is, the number of mammary cells suspended in collagen gels, with each cell dose labeled i. On the basis of the results of their LDTAs, the authors claimed that the CFCs originate from a single cell (the MRU), and this statement was supported by a standard chi-squared test (Pearson's χ2 statistic) providing high consistency with the SHPM for each LDTA. To endorse the appropriate use of χ2 statistics in their LDTAs, Eirew et al.1 cited an original statistical method previously published by us3 dealing with statistical modeling of limiting dilution data. Unfortunately, we cannot sanction the citation of our work in their article. The reason is that the scientific content of our paper has not been correctly used. This raises serious concerns about the decision to use χ2 statistic approach for analysis of LDTAs, which, in turn, raises questions concerning the biological conclusions drawn from the studies of Eirew et al.1.

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References

  1. Eirew, P. et al. Nat. Med. 14, 1384–1389 (2008).

    Article  CAS  Google Scholar 

  2. Porter, E.H. & Berry, R.J. Br. J. Cancer 17, 583–595 (1963).

    Article  CAS  PubMed Central  Google Scholar 

  3. Bonnefoix, T., Bonnefoix, P., Verdiel, P. & Sotto, J.J. J. Immunol. Methods 194, 113–119 (1996).

    Article  CAS  PubMed Central  Google Scholar 

  4. McCullagh, P. & Nelder, J.A. Generalized Linear Models. Chs. 2 and 4 (Chapman & Hall, London, 1989).

    Book  Google Scholar 

  5. Collett, D. Modelling Binary Data. Ch. 3 (Chapman & Hall, Boca Raton, Florida, 2003).

    Google Scholar 

  6. Agresti, A. Categorical Data Analysis. 77–78 (Wiley & Sons, Hoboken, New Jersey, 2002).

    Book  Google Scholar 

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Authors and Affiliations

  1. INSERM, U823, Oncogenic Pathways in the Haematological Malignancies, Institut Albert Bonniot, Grenoble, France

    Thierry Bonnefoix & Mary Callanan

  2. Université Joseph Fourier-Grenoble I, Faculté de Médecine, Institut Albert Bonniot, Grenoble, UMR-S823, France

    Thierry Bonnefoix & Mary Callanan

  3. Pôle de Recherche et Pôle de Biologie, Cellular and Molecular Haematology Unit, Plateforme Hospitalière de Génétique Moléculaire des Tumeurs, Centre Hospitalier Universitaire de Grenoble, France

    Thierry Bonnefoix & Mary Callanan

Authors
  1. Thierry Bonnefoix
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  2. Mary Callanan
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Correspondence to Thierry Bonnefoix.

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Bonnefoix, T., Callanan, M. Reassessing the human mammary stem cell concept by modeling limiting dilution transplantation assays. Nat Med 15, 602–604 (2009). https://doi.org/10.1038/nm0609-602b

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