Synthetic gene circuits and cellular decision-making in human pluripotent stem cells

Precise manipulation of human cell fate is a long-standing goal in biological engineering; it underpins efforts to advance new cellular therapeutics, and to develop disease models for fundamental research. Human pluripotent stem cells (hPSC) are emerging as the cells of choice for many of these applications. Currently, most advanced methods for manipulation of hPSC fate involve recapitulating developmental processes by mimicking stem cell niche-associated signals. Alternately, advances in engineering synthetic decision-making gene circuits provide an approach in which cell fate is directly controlled at the gene expression level. Here, we make the case that integrating these two engineering approaches represents an exciting opportunity to advance our fundamental understanding of cell fate control, and to accelerate new engineering strategies to manipulate cellular behavior for therapy.