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Stem cell proliferation and differentiation and stochastic bistability in gene expression

  • Statistical, Nonlinear, and Soft Matter Physics
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Abstract

The process of proliferation and differentiation of stem cells is inherently stochastic in the sense that the outcome of cell division is characterized by probabilities that depend on the intracellular properties, extracellular medium, and cell-cell communication. Despite four decades of intensive studies, the understanding of the physics behind this stochasticity is still limited, both in details and conceptually. Here, we suggest a simple scheme showing that the stochastic behavior of a single stem cell may be related to (i) the existence of a short stage of decision whether it will proliferate or differentiate and (ii) control of this stage by stochastic bistability in gene expression or, more specifically, by transcriptional “bursts.” Our Monte Carlo simulations indicate that our proposed scheme may operate if the number of mRNA (or protein) molecules generated during the high-reactive periods of gene expression is below or about 50. The stochastic-burst window in the space of kinetic parameters is found to increase with decreasing the mRNA and/or regulatory-protein numbers and increasing the number of regulatory sites. For mRNA production with three regulatory sites, for example, the mRNA degradation rate constant may change in the range ±10%.

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References

  1. J. E. Till and E. A. McCulloch, Radiat. Res. 14, 213 (1961).

    Article  Google Scholar 

  2. L. Alonso and E. Fuchs, Proc. Natl. Acad. Sci. USA 100 (Suppl. 1), 11830 (2003).

  3. J. I. Gordon, G. H. Schmidt, and K. A. Roth, FASEB J. 6, 3039 (1992).

    Google Scholar 

  4. C. Lois and A. Alvarezbuylla, Proc. Natl. Acad. Sci. USA 90, 2074 (1993); C. Klein and G. Fishell, Dev. Neurosci. 26, 82 (2004).

    Article  ADS  Google Scholar 

  5. N. Dewitt (Ed.), Nature 414, 87 (2001); A. Spradling, D. Drummond-Barbosa, and T. Kai, Nature 414, 98 (2001).

  6. N. L. Parenteau and J. H. Young, Ann. (N.Y.) Acad. Sci. 961, 27 (2002); M. Sykes and B. Nikolic, Nature 435, 620 (2005); C. Zandonella, Nature 435, 877 (2005).

    Article  ADS  Google Scholar 

  7. F. Ulloy-Montoya, C. M. Verfaillie, and W.-S. Hu, J. Biosci. Bioing. 100, 12 (2005).

    Article  Google Scholar 

  8. L. Siminovitch, E. A. McCulloch, and J. E. Till, J. Cell. Comp. Physiol. 62, 327 (1963); J. E. Till, L. Siminovitch, and E. A. McCulloch, Proc. Natl. Acad. Sci. USA 51, 29 (1964).

    Article  Google Scholar 

  9. S. Viswanathan and P. W. Zandstra, Cytotechnology 41, 75 (2003); A. O’Neill and D. V. Schaffer, Biotechnol. Appl. Biochem. 40, 5 (2004).

    Article  Google Scholar 

  10. V. P. Zhdanov and B. Kasemo, Phys. Chem. Chem. Phys. 6, 138 (2004); 4347 (2004); V. P. Zhdanov, D. Steel, B. Kasemo, and J. Gold, Phys. Chem. Chem. Phys. 7, 3496 (2005).

    Article  Google Scholar 

  11. K. Kaneko and T. Yomo, Bull. Math. Biol. 59, 139 (1997); C. Furusawa and K. Kaneko, Bull. Math. Biol. 60, 659 (1998); J. Theor. Biol. 224, 413 (2003); H. Yoshida, C. Furusawa, and K. Kaneko, J. Theor. Biol. 233, 501 (2005).

    Article  MATH  Google Scholar 

  12. H. D. Preisler and S. Kauffman, Leuk Res. 23, 685 (1999).

    Article  Google Scholar 

  13. S. Y. Shvartsman, AIChE J. 51, 1312 (2005).

    Article  Google Scholar 

  14. B. Schoeberl, C. Eichler-Jonsson, E. D. Gilles, and G. Müller, Nat. Biotechnol. 20, 370 (2002).

    Article  Google Scholar 

  15. C. Athale, Y. Mansury, and T. S. Deisboeck, J. Theor. Biol. 233, 469 (2005).

    Article  Google Scholar 

  16. J. E. Ferrell, Trends Biochem. Sci. 23, 461 (1998); J. E. Ferrell and W. Xiong, Chaos 11, 227 (2001).

    Article  Google Scholar 

  17. U. S. Bhalla and R. Iyengar, Chaos 11, 211 (2001); U. S. Bhalla, Prog. Biophys. Mol. Biol. 81, 45 (2003).

    Article  ADS  Google Scholar 

  18. J. Hasty, J. Pradines, M. Dolnik, and J. J. Collins, Proc. Natl. Acad. Sci. USA 97, 2075 (2000); M. Thattai and A. van Oudemaarden, Proc. Natl. Acad. Sci. USA 98, 8614 (2001); T. Shibata, Phys. Rev. E 67, 061906 (2003); Q. Liu and Y. Jan, Phys. Rev. E 70, 041907 (2004); Y. Morishita, T. Kobayashi, and K. Aihara, J. Theor. Biol. 235, 241 (2005); V. P. Zhdanov, Chem. Phys. Lett. 424, 394 (2006).

    Article  ADS  Google Scholar 

  19. L. Mariani, M. Löhning, A. Radbruch, and T. Höfer, Prog. Biophys. Mol. Biol. 86, 45 (2004).

    Article  Google Scholar 

  20. J. Paulsson, Nature 427, 415 (2004); S. Bornholdt, Science 310, 449 (2005).

    Article  ADS  Google Scholar 

  21. M. Kaern, T. C. Elston, W. J. Blake, and J. J. Collins, Nature Rev. Genet. 6, 451 (2005).

    Article  Google Scholar 

  22. J. Yu, J. Xiao, X. Ren, et al., Science 311, 1600 (2006).

    Article  ADS  Google Scholar 

  23. Computational Modeling of Genetic and Biochemical Networks, Ed. by J. M. Bower and H. Bolouri (MIT Press, London, 2001).

    Google Scholar 

  24. A. Arkin, J. Ross, and H. H. McAdams, Genetics 149, 1633 (1998); A. de Raniery, A. S. Virdi, S. Kuroda, et al., Bone 36, 931 (2005); O. Kobiler, A. Rokney, N. Friedman, et al., Proc. Natl. Acad. Sci. USA 102, 4470 (2005).

    Google Scholar 

  25. H. de Jong, J. Comput. Biol. 9, 67 (2002); M. P. Styczynski and G. Stephanopolos, Comput. Chem. Eng. 29, 519 (2005); R. Guthke, U. Moller, M. Hoffmann, et al., Bioinformatics 21, 1626 (2005); K. Noto and M. Craven, Reg. Genom. Lect. Notes Comput. Sci. 3318, 52 (2005); M. Lappe and L. Holm, Biochem. Soc. Trans. 33, 530 (2005); Y. Kaznessis, Chem. Eng. Sci. 61, 940 (2006).

    Article  Google Scholar 

  26. A. Paldi, Cell Mol. Life Sci. 60, 1775 (2003); A. Kurakin, Dev. Genes Evol. 215, 46 (2005).

    Article  Google Scholar 

  27. K. Birnbaum, D. E. Shasha, J. Y. Wang, et al., Science 302, 1956 (2003); M. Schmidt, T. S. Davison, S. R. Hertz, et al., Nat. Genet. 37, 501 (2005); B. J. DeYoung, K. L. Bickle, K. J. Schrage, et al., Plant J. 45, 1 (2006).

    Article  ADS  Google Scholar 

  28. L. S. Campos, J. Neurosci. Res. 78, 761 (2004).

    Article  Google Scholar 

  29. R. E. Gross, M. F. Mehler, P. C. Mabie, et al., Neuron 17, 595 (1996); A. Bonni, Y. Sun, M. Nada-Vicens, et al., Science 278, 477 (1997); P. Rajan and R. D. G. McKay, J. Neurosci. 18, 3620 (1998); K. Nakashima, T. Takitawa, W. Ochiai, et al., Proc. Natl. Acad. Sci. USA 98, 5868 (2001); M.-Y. Chang, H. Son, Y.-S. Lee, and S.-H. Lee, Mol. Cell Neurosci. 23, 414 (2003).

    Article  Google Scholar 

  30. U. Gurok, C. Steinhoff, B. Lipkovitz, et al., J. Neurosci. 24, 5982 (2004).

    Article  Google Scholar 

  31. T. Burdon, A. Smith, and P. Savatier, Trends Cell Biol. 12, 432 (2002).

    Article  Google Scholar 

  32. B. Alberts, A. Johnson, J. Lewis, et al., Molecular Biology of the Cell, 4th (Garland Sci., New York, 2002).

    Google Scholar 

  33. D. P. Landau and K. Binder, A Guide to Monte Carlo Simulations in Statistical Physics (Cambridge Univ. Press, Cambridge, 2000).

    MATH  Google Scholar 

  34. V. P. Zhdanov (unpublished).

  35. M. Pineda, R. Imbihl, L. Schimansky-Geier, and Ch. Zülicke, J. Chem. Phys. 124, 044701 (2006).

    Google Scholar 

  36. O. Cinquin and J. Demongeot, J. Theor. Biol. 233, 391 (2005).

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Applied Physics, Chalmers University of Technology, S-41296, Gothenburg, Sweden

    V. P. Zhdanov

  2. Boreskov Institute of Catalysis, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    V. P. Zhdanov

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  1. V. P. Zhdanov
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Zhdanov, V.P. Stem cell proliferation and differentiation and stochastic bistability in gene expression. J. Exp. Theor. Phys. 104, 162–169 (2007). https://doi.org/10.1134/S1063776107010165

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  • DOI: https://doi.org/10.1134/S1063776107010165

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