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Purpose of review: Strategies to manipulate stem cells for therapeutic applications are limited by our inability to control or predict stem cell fate decisions in response to exogenous stimuli. This review focuses on the mechanisms by which exogenous stimuli influence cell fate.

Recent findings: Limitations in our ability to control cell fate arises from our primarily qualitative understanding of stem cell regulation, which proposes straightforward cue-fate relationships that appear to be the exception rather than the rule. Alternatively, consideration of the underlying quantitative, temporal, and spatial mechanisms governing extrinsic regulation of stem cell fate may enable novel approaches to control stem cell output predictively.

Summary: The authors review advances in the understanding of these underlying mechanisms, and discuss experimental and analytic tools necessary to investigate and use these mechanisms to control stem cell fate.

(C) 2004 Lippincott Williams & Wilkins, Inc.