Emergent dynamics of thymocyte development and lineage determination

PLoS Comput Biol. 2007 Jan 26;3(1):e13. doi: 10.1371/journal.pcbi.0030013. Epub 2006 Dec 11.

Abstract

Experiments have generated a plethora of data about the genes, molecules, and cells involved in thymocyte development. Here, we use a computer-driven simulation that uses data about thymocyte development to generate an integrated dynamic representation-a novel technology we have termed reactive animation (RA). RA reveals emergent properties in complex dynamic biological systems. We apply RA to thymocyte development by reproducing and extending the effects of known gene knockouts: CXCR4 and CCR9. RA simulation revealed a previously unidentified role of thymocyte competition for major histocompatability complex presentation. We now report that such competition is required for normal anatomical compartmentalization, can influence the rate of thymocyte velocities within chemokine gradients, and can account for the disproportion between single-positive CD4 and CD8 lineages developing from double-positive precursors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Chemokines / metabolism
  • Chemotaxis / physiology*
  • Computer Simulation
  • Gene Expression Regulation, Developmental / physiology*
  • Humans
  • Models, Biological*
  • Receptors, CCR
  • Receptors, CXCR4 / metabolism*
  • Receptors, Chemokine / metabolism*
  • Thymus Gland / cytology*
  • Thymus Gland / physiology*

Substances

  • CC chemokine receptor 9
  • Chemokines
  • Receptors, CCR
  • Receptors, CXCR4
  • Receptors, Chemokine