Computational Screening of Tip and Stalk Cell Behavior Proposes a Role for Apelin Signaling in Sprout Progression

摘要: Angiogenesis involves the formation of new blood vessels by sprouting or splitting existing vessels. During sprouting, a highly motile type endothelial cell, called tip migrates from followed stalk cells, an cell that forms body sprout. To get more insight into how cells contribute to angiogenesis, we extended computational model vascular network based on cellular Potts with and differentiation, without making priori assumptions about differences between cells. predict potential differences, looked for parameter values make (a) move sprout tip, (b) change morphology angiogenic networks. The screening predicted if respond less effectively chemoattractant than they tips sprouts, which impacts A comparison this prediction genes expressed differentially in revealed Apelin its receptor APJ may match prediction. test inhibited signaling our vitro found both cases inhibition reduces sprouting. Based model, propose differential expression yields "self-generated" gradient mechanisms accelerates extension