Stem cell functions are regulated by a combination of molecular signals that are provided both intrinsically and from the local microenvironment. The complexity of these mechanisms has encouraged the use of interdisciplinary experimental strategies, such as bioengineering methods, to address fundamental questions in stem cell biology. These approaches have primarily aimed to (1) develop tools for the improved control of microenvironmental cues and genetic perturbations, (2) integrate high-throughput technologies to broaden the experimental state space and facilitate systematic examination of combinatorial signals, and (3) construct systems-based models to better define stem cell processes through an understanding of the interdependence of the individual signaling components. Cooperative advancements in these areas will continue to contribute to the evolution of stem cell-based therapeutics. WIREs Syst Biol Med 2012, 4:525–545. doi: 10.1002/wsbm.1189
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