TY - JOUR
T1 - Emergent dynamics of thymocyte development and lineage determination
AU - Efroni, Sol
AU - Harel, David
AU - Cohen, Irun R.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33846542982&partnerID=8YFLogxK
U2 - 10.1371/journal.pcbi.0030013
DO - 10.1371/journal.pcbi.0030013
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C2 - 17257050
AN - SCOPUS:33846542982
SN - 1553-734X
VL - 3
SP - 127
EP - 136
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 1
ER -