Probing Stem Cell Differentiation with Synthetic Biology

The demand for stem cells is anticipated to continue to rise due to their expected ability to treat disease, use in novel diagnostic technologies, and for pharmaceutical screening. However, before these goals can be realized, a better understanding of the mechanisms regulating their fate is required. Cells have the remarkable ability to continuously sense, integrate, and store relevant physiological and biological information throughout their lives. They integrate the many signals that surround them and execute cellular behaviors based on these inputs. Both intrinsic (transcription factor expression), as well as extrinsic (environmental) mechanisms are thought to be involved in the regulation of stem cell self-renewal, and their commitment to differentiate into more specialized cell types. This interplay between intrinsic and extrinsic cues in differentiation poses challenges to studying the mechanisms involved in their proliferation and terminal differentiation. These challenges can be addressed using genetic circuits to tightly control gene expression in dynamic patterns, in addition to programming cells to sense and record changes in their microenvironment as cells undergo differentiation.