title: Spatial and temporal dynamics of cell generations within an invasion wave: a link to cell lineage tracing.
abstract: Mathematical models of a cell invasion wave have included both continuum partial differential equation (PDE) approaches and discrete agent-based cellular automata (CA) approaches. Here we are interested in modelling the spatial and temporal dynamics of the number of divisions (generation number) that cells have undergone by any time point within an invasion wave. In the CA framework this is performed from agent lineage tracings, while in the PDE approach a multi-species generalized Fisher equation is derived for the cell density within each generation. Both paradigms exhibit qualitatively similar cell generation densities that are spatially organized, with agents of low generation number rapidly attaining a steady state (with average generation number increasing linearly with distance) behind the moving wave and with evolving high generation number at the wavefront. This regularity in the generation spatial distributions is in contrast to the highly stochastic nature of the underlying lineage dynamics of the population. In addition, we construct a method for determining the lineage tracings of all agents without labelling and tracking the agents, but through either a knowledge of the spatial distribution of the generations or the number of agents in each generation. This involves determining generation-dependent proliferation probabilities and using these to define a generation-dependent Galton-Watson (GDGW) process. Monte-Carlo simulations of the GDGW process are used to determine the individual lineage tracings. The lineages of the GDGW process are analyzed using Lorenz curves and found to be similar to outcomes generated by direct lineage tracing in CA realizations. This analysis provides the basis for a potentially useful technique for deducing cell lineage data when imaging every cell is not feasible.
authors.affiliation: Department of Mathematics and Statistics, University of Melbourne, Victoria 3010, Australia.
authors.forename: Bevan L
authors.initials: BL
authors.lastname: Cheeseman
authors.affiliation: Murdoch Childrens Research Institute, Royal Children׳s Hospital, Parkville, Victoria 3052 Australia.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Newgreen
authors.affiliation: Department of Mathematics and Statistics, University of Melbourne, Victoria 3010, Australia. Electronic address: kerryl@unimelb.edu.au.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Landman
mesh_terms: D002455:Cell Division / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D003198:Computer Simulation; D017615:Enteric Nervous System / Q000254:growth & development*; D006801:Humans; D008954:Models, Biological; D009432:Neural Crest / Q000502:physiology*
keywords: Agent-based model; Cell invasion; Continuum multispecies model; Fisher wave; Galton–Watson process