Single-cell variability in multicellular organisms.

Stephen Smith, Ramon Grima
Author Information
  1. Stephen Smith: School of Biological Sciences, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR, Scotland, UK.
  2. Ramon Grima: School of Biological Sciences, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR, Scotland, UK. ramon.grima@ed.ac.uk.

Abstract

Noisy gene expression is of fundamental importance to single cells, and is therefore widely studied in single-celled organisms. Extending these studies to multicellular organisms is challenging since their cells are generally not isolated, but individuals in a tissue. Cell-cell coupling via signalling, active transport or pure diffusion, ensures that tissue-bound cells are neither fully independent of each other, nor an entirely homogeneous population. In this article, we show that increasing the strength of coupling between cells can either increase or decrease the single-cell variability (and, therefore, the heterogeneity of the tissue), depending on the statistical properties of the underlying genetic network. We confirm these predictions using spatial stochastic simulations of simple genetic networks, and experimental data from animal and plant tissues. The results suggest that cell-cell coupling may be one of several noise-control strategies employed by multicellular organisms, and highlight the need for a deeper understanding of multicellular behaviour.

References

  1. Science. 2004 Sep 10;305(5690):1622-5 [PMID: 15308767]
  2. Cell. 1993 Jul 30;74(2):309-18 [PMID: 8343958]
  3. J Chem Phys. 2006 Jan 28;124(4):044104 [PMID: 16460146]
  4. Cell. 2008 Oct 17;135(2):216-26 [PMID: 18957198]
  5. Plant Physiol. 2001 Apr;125(4):1802-12 [PMID: 11299360]
  6. Science. 1995 Dec 22;270(5244):1980-3 [PMID: 8533088]
  7. Nature. 2006 Jun 22;441(7096):1011-4 [PMID: 16791200]
  8. Science. 2007 Jul 27;317(5837):526-9 [PMID: 17569828]
  9. Curr Biol. 2000 Sep 7;10(17):1032-40 [PMID: 10996070]
  10. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1996 Dec;54(6):6139-6148 [PMID: 9965833]
  11. J R Soc Interface. 2016 May;13(118): [PMID: 27146686]
  12. Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6757-62 [PMID: 22496591]
  13. Mol Cell. 2015 Apr 2;58(1):147-56 [PMID: 25728770]
  14. Phys Biol. 2009 Aug 21;6(4):046001 [PMID: 19700812]
  15. Proc Natl Acad Sci U S A. 2014 May 13;111(19):6994-9 [PMID: 24782538]
  16. Cell. 1996 Feb 9;84(3):381-8 [PMID: 8608591]
  17. Mol Biol Cell. 2003 Jul;14(7):2768-80 [PMID: 12857863]
  18. Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):814-9 [PMID: 9023339]
  19. Science. 2002 Aug 16;297(5584):1183-6 [PMID: 12183631]
  20. Cell. 2007 Nov 2;131(3):544-56 [PMID: 17981121]
  21. Elife. 2016 Feb 01;5:e08494 [PMID: 26828110]
  22. Nature. 2004 Feb 19;427(6976):737-40 [PMID: 14973486]
  23. PLoS One. 2012;7(3):e33334 [PMID: 22479387]
  24. Phys Rev E Stat Nonlin Soft Matter Phys. 2001 May;63(5 Pt 2):056124 [PMID: 11414978]
  25. Phys Rev E. 2016 May;93(5):052135 [PMID: 27300857]
  26. Nat Protoc. 2013 Sep;8(9):1743-58 [PMID: 23949380]
  27. PLoS One. 2011;6(12):e27886 [PMID: 22194797]
  28. Cell. 2011 Aug 19;146(4):633-44 [PMID: 21854987]
  29. BMC Syst Biol. 2010 Mar 26;4:34 [PMID: 20346112]
  30. Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17256-61 [PMID: 18988743]
  31. Nature. 2006 Mar 9;440(7081):174-80 [PMID: 16525464]
  32. Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17194-9 [PMID: 20855598]
  33. J Chem Phys. 2012 Apr 21;136(15):154105 [PMID: 22519313]

MeSH Term

Animals
Arabidopsis
Cell Communication
Fibroblasts
Gene Regulatory Networks
Green Fluorescent Proteins
Mice
Models, Biological
Pituitary Gland
Plant Leaves
Rats
Stochastic Processes

Chemicals

Green Fluorescent Proteins

Word Cloud

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