Modulating signals to pattern complex tissues*

The blastocyst of the human embryo forms a single-layer epithelial sheet of cells called the epiblast. This epiblast gives rise to the entire human body over the course of development. The patterning of the epiblast is achieved through a sequence of symmetry-breaking events driven by signals. The identity of the signals is often known. However, their spatiotemporal profiles, certainly in the case of human embryos and, more broadly, for most vertebrate embryos, are not. One might think of these morphogen signal profiles as establishing boundary conditions for a complex underlying dynamical system, driving it to pattern itself. 

Embryonic stem cells are obtained from the blastocyst of the embryo and can be cultured indefinitely. These cells have the capability to generate all the cell types of the body. Can we pattern these cells by learning and establishing the correct spatiotemporal boundary conditions to generate complex human tissues? We will address this question using a combination of statistical inference approaches and experiments on human embryonic stem cells.