Inducing pluripotency, the capacity to differentiate into any cell type, has become a vital tool for biomedical research. It is achieved through exogenous expression of pluripotency-inducing factors as a “reprogramming cocktail,” which triggers massive changes that erase a cell’s previous identity and install a new, pluripotent identity. The ability to experimentally manipulate cellular identity has enormous implications for disease modeling and therapies; yet, it remains a highly inefficient process in the laboratory. In contrast, transcriptional reprogramming in its endogenous context, the developing embryo, is stereotypical and efficient. The goal of Lee’s lab is to better understand pluripotency induction by characterizing the ways endogenous reprogramming cocktails in the egg guide early development.
To identify the gene targets of vertebrate pluripotency factors, Lee and colleagues have built regulatory maps of the zebrafish and Xenopus laevis embryonic genomes. They observe surprising diversity in the regulatory architecture, much of which appears to have been driven by viral-like sequences called transposable elements. Upon insertion into novel genetic contexts, these transposable elements can, over time, direct pluripotency factors to activate new genes, thus rewiring the regulatory networks underlying pluripotency induction. These findings contribute to Lee’s efforts to elucidate gene regulatory paradigms across embryos and gain a deeper understanding of how a pluripotent identity can be induced in any cell.