4D dynamics of mouse embryonic stem cell self-organization

Trabajo presentado en Decision Making in Cell Collectives Launching Meeting, cleebrado en Carmona (España) del 5 al 6 de abril de 2018.Mouse embryonic stem cells can be kept uniformly pluripotent in tissue culture, and they spontaneously form segregated germ layers in ¿embryoid bodies¿ in the absence of pluripotency factors. The localized expression of germ layer markers resembles the formation of the anterior-posterior axis in mouse embryos, but the mechanistic basis of this self-organizing process has remained enigmatic. Here, we have analyzed the spatiotemporal dynamics of symmetry breaking in embryoid bodies using light-sheet microscopy. Our data shows that the formation of the anterior-posterior axis is characterized by a moving front of mesendodermal fates that propagates from the boundary of embryoid bodies. We constructed a three-dimensional computational model of embryoid body formation, and we show that the spatiotemporal dynamics of self-organization can be recapitulated by a bistable reaction-diffusion mechanism. In agreement with the predictions of the model, our data demonstrates that self-organized axis formation is size-independent and that the front velocity is controlled by Wnt and Nodal signaling