Figure 3. Constructing simple synthetic developmental networks with modular cell-cell interaction.

(A) Schematic illustration of engineering self-organizing multi-layered spheroids. Sender cells expressing a ligand (blue) induce a synNotch-expressing receiver cell(green) to cell(green) to express homotypic adhesion molecule (yellow) and heterotypic adhesion molecule (red). When we mix these cell types together, the cell population starts to organize to form a core aggregate of receiver cells surrounded by sender cells (blue).

(B) Examples of user-defined organizers. (Left) Shh-producing hPSC aggregate is used as a local source of Shh, acting as one pole of the developing forebrain organoid. (Right) Strategy to generate a Wnt and Nodal gradient in an embryoid model. mESCs treated with BMP4 are used as an engineered morphogen signaling center. mESCs close to the signaling center differentiate into mesoderm, resembling the posterior region of a mouse embryo.

(C) The synthetic diffusible communication system generates an artificial morphogen gradient. By modulating expression levels of morphogens, we can tune the gradient patters (right).