Coalescent models for developmental biology and the spatio-temporal dynamics of growing tissues

Development is a process that needs to be tightly coordinated in both space and time. Cell tracking and lineage tracing have become important experimental techniques in developmental biology and allow us to map the fate of cells and their progeny. A generic feature of developing and homeostatic tissues that these analyses have revealed is that relatively few cells give rise to the bulk of the cells in a tissue; the lineages of most cells come to an end quickly. Computational and theoretical biologists/physicists have, in response, developed a range of modelling approaches, most notably agent-based modelling. These models seem to capture features observed in experiments, but can also become computationally expensive. Here, we develop complementary genealogical models of tissue development that trace the ancestry of cells in a tissue back to their most recent common ancestors. We show that with both bounded and unbounded growth simple, but universal scaling relationships allow us to connect coalescent theory with the fractal growth models extensively used in developmental biology. Using our genealogical perspective, it is possible to study bulk statistical properties of the processes that give rise to tissues of cells, without the need for large-scale simulations.

[1]  Dynamical scaling behavior in two-dimensional ballistic deposition with shadowing. , 2002, Physical review. E, Statistical, nonlinear, and soft matter physics.

[2]  Simon Tavaré,et al.  Integrating Approximate Bayesian Computation with Complex Agent-Based Models for Cancer Research , 2010, COMPSTAT.

[3]  Charles M. Macal,et al.  Tutorial on agent-based modeling and simulation , 2005 .

[4]  J. Cardy Scaling and Renormalization in Statistical Physics , 1996 .

[5]  Kerry A Landman,et al.  Modeling biological tissue growth: discrete to continuum representations. , 2013, Physical review. E, Statistical, nonlinear, and soft matter physics.

[6]  J. Sulston,et al.  The embryonic cell lineage of the nematode Caenorhabditis elegans. , 1983, Developmental biology.

[7]  H. Clevers,et al.  Biased competition between Lgr5 intestinal stem cells driven by oncogenic mutation induces clonal expansion , 2013, EMBO reports.

[8]  H M Byrne,et al.  A multiscale analysis of nutrient transport and biological tissue growth in vitro. , 2015, Mathematical medicine and biology : a journal of the IMA.

[9]  Nan Chen,et al.  A Parallel Implementation of the Cellular Potts Model for Simulation of Cell-Based Morphogenesis , 2006, ACRI.

[10]  J White,et al.  Four-Dimensional Imaging: Computer Visualization of 3D Movements in Living Specimens , 1996, Science.

[11]  A. Barabasi,et al.  Fractal Concepts in Surface Growth: Frontmatter , 1995 .

[12]  Noah A. Rosenberg,et al.  Genealogical trees, coalescent theory and the analysis of genetic polymorphisms , 2002, Nature Reviews Genetics.

[13]  A. Bunde,et al.  From the eden model to the kinetic growth walk: A generalized growth model with a finite lifetime of growth sites , 1987 .

[14]  Bevan L. Cheeseman,et al.  Cell lineage tracing in the developing enteric nervous system: superstars revealed by experiment and simulation , 2014, Journal of The Royal Society Interface.

[15]  R. Botet,et al.  SCALING PROPERTIES OF THE SURFACE OF THE EDEN MODEL , 1986 .

[16]  R. Griffiths,et al.  Lines of descent in the diffusion approximation of neutral Wright-Fisher models. , 1980, Theoretical population biology.

[17]  Michael J. North,et al.  Tutorial on agent-based modelling and simulation , 2005, Proceedings of the Winter Simulation Conference, 2005..

[18]  F. Watt,et al.  Lineage Tracing , 2012, Cell.

[19]  E. D. Robertis,et al.  Spemann's organizer and self-regulation in amphibian embryos , 2006, Nature Reviews Molecular Cell Biology.

[20]  Yun-Xin Fu Exact coalescent for the Wright-Fisher model. , 2006, Theoretical population biology.

[21]  J. Sharpe,et al.  Positional information and reaction-diffusion: two big ideas in developmental biology combine , 2015, Development.

[22]  M. Slatkin,et al.  Pairwise comparisons of mitochondrial DNA sequences in stable and exponentially growing populations. , 1991, Genetics.

[23]  M. Kimura,et al.  The Stepping Stone Model of Population Structure and the Decrease of Genetic Correlation with Distance. , 1964, Genetics.

[24]  Stephen M. Krone,et al.  Separation of time scales and convergence to the coalescent in structured populations ∗ , 2001 .

[25]  A. Barabasi,et al.  Fractal concepts in surface growth , 1995 .

[26]  R. Jullien,et al.  Scaling properties of the surface of the Eden model in d=2, 3, 4 , 1985 .

[27]  R. Nielsen,et al.  Distinguishing migration from isolation: a Markov chain Monte Carlo approach. , 2001, Genetics.

[28]  W. Ewens Mathematical Population Genetics , 1980 .

[29]  Zhang,et al.  Dynamic scaling of growing interfaces. , 1986, Physical review letters.

[30]  C. J-F,et al.  THE COALESCENT , 1980 .

[31]  Carsten Wiuf,et al.  Gene Genealogies, Variation and Evolution - A Primer in Coalescent Theory , 2004 .

[32]  Stauffer,et al.  Simulation of large Eden clusters. , 1986, Physical review. A, General physics.

[33]  A. Hansen,et al.  A direct mapping between Eden growth model and directed polymers in random media , 1991 .

[34]  Maritan,et al.  Invasion percolation and Eden growth: Geometry and universality. , 1996, Physical review letters.

[35]  Heather A. Harrington,et al.  Nuclear to cytoplasmic shuttling of ERK promotes differentiation of muscle stem/progenitor cells , 2014, Development.

[36]  Eden growth model for aggregation of charged particles , 1998, cond-mat/9806345.

[37]  Mitsugu Matsushita,et al.  Morphological Changes in Growth Phenomena of Bacterial Colony Patterns , 1992 .

[38]  A. Tellier,et al.  Coalescence 2.0: a multiple branching of recent theoretical developments and their applications , 2014, bioRxiv.

[39]  F. Tajima Evolutionary relationship of DNA sequences in finite populations. , 1983, Genetics.

[40]  Hans Clevers,et al.  Intestinal Crypt Homeostasis Results from Neutral Competition between Symmetrically Dividing Lgr5 Stem Cells , 2010, Cell.

[41]  Kerry A Landman,et al.  Exclusion processes on a growing domain. , 2009, Journal of theoretical biology.

[42]  S. Tavaré,et al.  Many colorectal cancers are “flat” clonal expansions , 2009, Cell cycle.

[43]  S. Fraser,et al.  Tracing the lineage of tracing cell lineages , 2001, Nature Cell Biology.

[44]  K. Korolev,et al.  Genetic demixing and evolution in linear stepping stone models. , 2010, Reviews of modern physics.

[45]  Juli'an Candia,et al.  The Magnetic Eden Model , 2008, 0806.4767.

[46]  Andrea Sottoriva,et al.  Defining Stem Cell Dynamics in Models of Intestinal Tumor Initiation , 2013, Science.

[47]  C. Curtis,et al.  A Big Bang model of human colorectal tumor growth , 2015, Nature Genetics.

[48]  Hans Clevers,et al.  Lineage Tracing Reveals Lgr5+ Stem Cell Activity in Mouse Intestinal Adenomas , 2012, Science.

[49]  L. Wolpert Positional information and the spatial pattern of cellular differentiation. , 1969, Journal of theoretical biology.

[50]  M. Eden A Two-dimensional Growth Process , 1961 .

[51]  Oskar Hallatschek,et al.  Genealogies of rapidly adapting populations , 2012, Proceedings of the National Academy of Sciences.

[52]  D. Wolf,et al.  Noise reduction in Eden models. I , 1987 .

[53]  E. D. De Robertis Spemann's organizer and self-regulation in amphibian embryos , 2006, Nature reviews. Molecular cell biology.

[54]  James Briscoe,et al.  A theoretical framework for the regulation of Shh morphogen-controlled gene expression , 2014, Development.

[55]  B. Derrida,et al.  Universal tree structures in directed polymers and models of evolving populations. , 2008, Physical review. E, Statistical, nonlinear, and soft matter physics.

[56]  W. Ewens Mathematical Population Genetics : I. Theoretical Introduction , 2004 .