Emergent dynamics of thymocyte development and lineage determination.
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.
Efroni
Sol
S
National Cancer Institute Center for Bioinformatics, National Institutes of Health, Rockville, Maryland, United States of America. sefroni@mail.nih.gov
Harel
David
D
Cohen
Irun R
IR
D000465:Algorithms; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology*; D003198:Computer Simulation; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D054388:Receptors, CCR; D019718:Receptors, CXCR4 / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000502:physiology*
C119309:CC chemokine receptor 9; D018925:Chemokines; D054388:Receptors, CCR; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine