Development Genes and Evolution

, Volume 215, Issue 1, pp 46–52

Self-organization vs Watchmaker: stochastic gene expression and cell differentiation

Hypothesis Paper

Abstract

Cell differentiation and organism development are traditionally described in deterministic terms of program and design, echoing a conventional clockwork perception of the cell on another scale. However, the current experimental reality of stochastic gene expression and cell plasticity is poorly consistent with the ideas of design, purpose and determinism, suggesting that the habit of classico-mechanistic interpretation of life phenomena may handicap our ability to adequately comprehend and model biological systems. An alternative conceptualization of cell differentiation and development is proposed where the developing organism is viewed as a dynamic self-organizing system of adaptive interacting agents. This alternative interpretation appears to be more consistent with the probabilistic nature of gene expression and the phenomena of cell plasticity, and is coterminous with the novel emerging image of the cell as a self-organizing molecular system. I suggest that stochasticity, as a principle of differentiation and adaptation, and self-organization, as a concept of emergence, have the potential to provide an interpretational framework that unites phenomena across different scales of biological organization, from molecules to societies.

Keywords

Stochasticity Self-organization Gene expression Cell differentiation Cell plasticity 

References

  1. Alison MR, Poulsom R, Jeffery R, Dhillon AP, Quaglia A, Jacob J, Novelli M, Prentice G, Williamson J, Wright NA (2000) Hepatocytes from non-hepatic adult stem cells. Nature 406:257CrossRefPubMedGoogle Scholar
  2. Beshers SN, Fewell JH (2001) Models of division of labor in social insects. Annu Rev Entomol 46:413–440CrossRefPubMedGoogle Scholar
  3. Biggar SR, Crabtree GR (2001) Cell signaling can direct either binary or graded transcriptional responses. EMBO J 20:3167–3176CrossRefPubMedGoogle Scholar
  4. Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL (1999) Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 283:534–537CrossRefPubMedGoogle Scholar
  5. Blake WJ, M KA, Cantor CR, Collins JJ (2003) Noise in eukaryotic gene expression. Nature 422:633–637CrossRefPubMedGoogle Scholar
  6. Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290:1775–1779CrossRefPubMedGoogle Scholar
  7. Chelly J, Concordet JP, Kaplan JC, Kahn A (1989) Illegitimate transcription: transcription of any gene in any cell type. Proc Natl Acad Sci USA 86:2617–2621PubMedGoogle Scholar
  8. Cheutin T, Gorski SA, May KM, Singh PB, Misteli T (2004) In vivo dynamics of Swi6 in yeast: evidence for a stochastic model of heterochromatin. Mol Cell Biol 24:3157–3167CrossRefPubMedGoogle Scholar
  9. Cook DL, Gerber AN, Tapscott SJ (1998) Modeling stochastic gene expression: implications for haploinsufficiency. Proc Natl Acad Sci USA 95:15641–15646CrossRefPubMedGoogle Scholar
  10. Dundr M, Hoffmann-Rohrer U, Hu Q, Grummt I, Rothblum LI, Phair RD, Misteli T (2002) A kinetic framework for a mammalian RNA polymerase in vivo. Science 298:1623–1626CrossRefPubMedGoogle Scholar
  11. Essers J, Houtsmuller AB, van Veelen L, Paulusma C, Nigg AL, Pastink A, Vermeulen W, Hoeijmakers JH, Kanaar R (2002) Nuclear dynamics of RAD52 group homologous recombination proteins in response to DNA damage. EMBO J 21:2030–2037CrossRefPubMedGoogle Scholar
  12. Femino AM, Fay FS, Fogarty K, Singer RH (1998) Visualization of single RNA transcripts in situ. Science 280:585–590CrossRefPubMedGoogle Scholar
  13. Fewell JH (2003) Social insect networks. Science 301:1867–1870CrossRefPubMedGoogle Scholar
  14. Fiering S, Northrop JP, Nolan GP, Mattila PS, Crabtree GR, Herzenberg LA (1990) Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor. Genes Dev 4:1823–1834PubMedGoogle Scholar
  15. Fiering S, Whitelaw E, Martin DI (2000) To be or not to be active: the stochastic nature of enhancer action. Bioessays 22:381–387PubMedGoogle Scholar
  16. Grande MA, van der Kraan I, de Jong L, van Driel R (1997) Nuclear distribution of transcription factors in relation to sites of transcription and RNA polymerase II. J Cell Sci 110(15):1781–1791PubMedGoogle Scholar
  17. Harris RG, Herzog EL, Bruscia EM, Grove JE, Van Arnam JS, Krause DS (2004) Lack of a fusion requirement for development of bone marrow-derived epithelia. Science 305:90–93CrossRefPubMedGoogle Scholar
  18. Herndon LA, Schmeissner PJ, Dudaronek JM, Brown PA, Listner KM, Sakano Y, Paupard MC, Hall DH, Driscoll M (2002) Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419:808–814CrossRefPubMedGoogle Scholar
  19. Ho SN, Biggar SR, Spencer DM, Schreiber SL, Crabtree GR (1996) Dimeric ligands define a role for transcriptional activation domains in reinitiation. Nature 382:822–826CrossRefPubMedGoogle Scholar
  20. Hoogstraten D, Nigg AL, Heath H, Mullenders LH, van Driel R, Hoeijmakers JH, Vermeulen W, Houtsmuller AB (2002) Rapid switching of TFIIH between RNA polymerase I and II transcription and DNA repair in vivo. Mol Cell 10:1163–1174CrossRefPubMedGoogle Scholar
  21. Hume DA (2000) Probability in transcriptional regulation and its implications for leukocyte differentiation and inducible gene expression. Blood 96:2323–2328PubMedGoogle Scholar
  22. Iborra FJ, Pombo A, Jackson DA, Cook PR (1996) Active RNA polymerases are localized within discrete transcription “factories’ in human nuclei. J Cell Sci 109(6):1427–1436PubMedGoogle Scholar
  23. Jouvenot Y, Poirier F, Jami J, Paldi A (1999) Biallelic transcription of Igf2 and H19 in individual cells suggests a post-transcriptional contribution to genomic imprinting. Curr Biol 9:1199–1202CrossRefPubMedGoogle Scholar
  24. Kimura H, Sugaya K, Cook PR (2002) The transcription cycle of RNA polymerase II in living cells. J Cell Biol 159:777–782CrossRefPubMedGoogle Scholar
  25. Ko MS, Nakauchi H, Takahashi N (1990) The dose dependence of glucocorticoid-inducible gene expression results from changes in the number of transcriptionally active templates. EMBO J 9:2835–2842PubMedGoogle Scholar
  26. Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105:369–377CrossRefGoogle Scholar
  27. Kringstein AM, Rossi FM, Hofmann A, Blau HM (1998) Graded transcriptional response to different concentrations of a single transactivator. Proc Natl Acad Sci USA 95:13670–13675CrossRefPubMedGoogle Scholar
  28. Kupiec JJ (1997) A Darwinian theory for the origin of cellular differentiation. Mol Gen Genet 255:201–208CrossRefPubMedGoogle Scholar
  29. Kurakin A (2004) Self-organization versus Watchmaker: stochasticity and determinism in molecular and cell biology. Available at http://www.alexeikurakin.org/text/ak030304.pdf
  30. Kuznetsov VA, Knott GD, Bonner RF (2002) General statistics of stochastic process of gene expression in eukaryotic cells. Genetics 161:1321–1332PubMedGoogle Scholar
  31. Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6:1229–1234CrossRefPubMedGoogle Scholar
  32. Levsky JM, Shenoy SM, Pezo RC, Singer RH (2002) Single-cell gene expression profiling. Science 297:836–840CrossRefPubMedGoogle Scholar
  33. Li L, Connelly MC, Wetmore C, Curran T, Morgan JI (2003) Mouse embryos cloned from brain tumors. Cancer Res 63:2733–2736PubMedGoogle Scholar
  34. Loeffler M, Roeder I (2002) Tissue stem cells: definition, plasticity, heterogeneity, self-organization and models—a conceptual approach. Cells Tissues Organs 171:8–26CrossRefPubMedGoogle Scholar
  35. Misteli T (2001) The concept of self-organization in cellular architecture. J Cell Biol 155:181–185CrossRefPubMedGoogle Scholar
  36. Misteli T, Gunjan A, Hock R, Bustin M, Brown DT (2000) Dynamic binding of histone H1 to chromatin in living cells. Nature 408:877–881CrossRefPubMedGoogle Scholar
  37. Morel B, Ramanujam R (1999) Through the looking glass of complexity: the dynamics of organizations as adaptive and evolving systems. Organ Sci 10:278–293Google Scholar
  38. Nedelec F, Surrey T, Karsenti E (2003) Self-organisation and forces in the microtubule cytoskeleton. Curr Opin Cell Biol 15:118–124CrossRefPubMedGoogle Scholar
  39. Newlands S, Levitt LK, Robinson CS, Karpf AB, Hodgson VR, Wade RP, Hardeman EC (1998) Transcription occurs in pulses in muscle fibers. Genes Dev 12:2748–2758PubMedGoogle Scholar
  40. Ogawa M (1993) Differentiation and proliferation of hematopoietic stem cells. Blood 81:2844–2853PubMedGoogle Scholar
  41. Paldi A (2003) Stochastic gene expression during cell differentiation: order from disorder? Cell Mol Life Sci 60:1775–1778CrossRefPubMedGoogle Scholar
  42. Roeder I, Loeffler M (2002) A novel dynamic model of hematopoietic stem cell organization based on the concept of within-tissue plasticity. Exp Hematol 30:853–861CrossRefPubMedGoogle Scholar
  43. Ross IL, Browne CM, Hume DA (1994) Transcription of individual genes in eukaryotic cells occurs randomly and infrequently. Immunol Cell Biol 72:177–185PubMedGoogle Scholar
  44. Rossi FM, Kringstein AM, Spicher A, Guicherit OM, Blau HM (2000) Transcriptional control: rheostat converted to on/off switch. Mol Cell 6:723–728CrossRefPubMedGoogle Scholar
  45. Sandaltzopoulos R, Becker PB (1998) Heat shock factor increases the reinitiation rate from potentiated chromatin templates. Mol Cell Biol 18:361–367PubMedGoogle Scholar
  46. Sasai M, Wolynes PG (2003) Stochastic gene expression as a many-body problem. Proc Natl Acad Sci USA 100:2374–2379CrossRefPubMedGoogle Scholar
  47. Serizawa S, Miyamichi K, Nakatani H, Suzuki M, Saito M, Yoshihara Y, Sakano H (2003) Negative feedback regulation ensures the one receptor-one olfactory neuron rule in mouse. Science 302:2088–2094CrossRefPubMedGoogle Scholar
  48. Takasuka N, White MR, Wood CD, Robertson WR, Davis JR (1998) Dynamic changes in prolactin promoter activation in individual living lactotrophic cells. Endocrinology 139:1361–1368CrossRefPubMedGoogle Scholar
  49. Thattai M, van Oudenaarden A (2001) Intrinsic noise in gene regulatory networks. Proc Natl Acad Sci USA 98:8614–8619CrossRefPubMedGoogle Scholar
  50. Theise ND, Krause DS (2002) Toward a new paradigm of cell plasticity. Leukemia 16:542–548CrossRefPubMedGoogle Scholar
  51. Theise ND, Wilmut I (2003) Cell plasticity: flexible arrangement. Nature 425:21CrossRefPubMedGoogle Scholar
  52. Tian XC (2004) Reprogramming of epigenetic inheritance by somatic cell nuclear transfer. Reprod Biomed Online 8:501–508PubMedGoogle Scholar
  53. Turcotte DL, Rundle JB (2002) Self-organized complexity in the physical, biological, and social sciences. Proc Natl Acad Sci USA 99(Suppl 1):2463–2465CrossRefPubMedGoogle Scholar
  54. Vendruscolo M, Zurdo J, MacPhee CE, Dobson CM (2003) Protein folding and misfolding: a paradigm of self-assembly and regulation in complex biological systems. Philos Trans Ser A Math Phys Eng Sci 361:1205–1222CrossRefGoogle Scholar
  55. Walters MC, Fiering S, Eidemiller J, Magis W, Groudine M, Martin DI (1995) Enhancers increase the probability but not the level of gene expression. Proc Natl Acad Sci USA 92:7125–7129PubMedGoogle Scholar
  56. Weintraub H (1988) Formation of stable transcription complexes as assayed by analysis of individual templates. Proc Natl Acad Sci USA 85:5819–5823PubMedGoogle Scholar
  57. White MR, Masuko M, Amet L, Elliott G, Braddock M, Kingsman AJ, Kingsman SM (1995) Real-time analysis of the transcriptional regulation of HIV and hCMV promoters in single mammalian cells. J Cell Sci 108(2):441–455PubMedGoogle Scholar
  58. Wurmser AE, Nakashima K, Summers RG, Toni N, D’Amour KA, Lie DC, Gage FH (2004) Cell fusion-independent differentiation of neural stem cells to the endothelial lineage. Nature 430:350–356CrossRefPubMedGoogle Scholar
  59. Xie XS, Lu HP (1999) Single-molecule enzymology. J Biol Chem 274:15967–15970CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Buck Institute for Age ResearchNovatoUSA

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