Synthetic developmental biology tools involve building systems that recapitulate developmental processes through spatial and temporal control of cellular behaviour. While many synthetic tools have been developed in different cell types, in this new study, Sarah Soliman, Zara Weinberg and colleagues characterise a collection of small molecule- and cell contact-inducible systems in mouse embryonic stem cells (mESCs). They adapt three drug-inducible systems and two juxtracrine cell contact-inducible systems for use in mESCs and test each system systematically. They demonstrate that these systems can induce gene expression in mESCs – in their case, a blue fluorescent protein reporter. Then, they test whether the small molecule systems can induce mESC differentiation into neurons by activating the pro-neural transcription factor neurogenin 2. Some, but not all the systems can drive mESC differentiation, suggesting the importance of choosing the best system according to the application and cell type. They also find that the juxtracrine-inducible system SNIPR can drive differentiation of mESCs into neurons in a cell contact- and spatially dependent manner. Overall, the study demonstrates an approach to engineer drug- and cell contact-inducible systems for controlling expression and differentiation in mESCs. The components and methods described can be adapted into building more complex synthetic systems, expanding the toolkit for studying developmental processes.

© 2025. Published by The Company of Biologists
2025