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WIREs Syst Biol Med
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Stem cell bioengineering at the interface of systems‐based models and high‐throughput platforms

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Abstract 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 This article is categorized under: Models of Systems Properties and Processes > Cellular Models Laboratory Methods and Technologies > Genetic/Genomic Methods Developmental Biology > Stem Cell Biology and Regeneration Translational, Genomic, and Systems Medicine > Translational Medicine

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Convergent methods for elucidating stem cell genetic programs. An understanding of the intrinsic signaling and gene regulatory mechanisms underlying stem cell function requires the comprehensive analysis and integration of gene expression profiles, protein–protein interactions, transcription factor–DNA binding localizations, miRNA expression and interaction data, and measurements of epigenetic state. Such studies have been enabled by numerous high‐throughput experimental methods, coupled with computational tools (light blue boxes). Emerging technologies and approaches (dark blue boxes) should aid further refinements in regulatory models, including insights at the single cell level, and facilitate an improved capacity for dictating stem cell fate through the controlled manipulation of regulatory programs.

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Engineering approaches for the study of stem cell microenvironments. Depicted are the prototypical components of a stem cell microenvironment, or niche. A network of interacting microenvironmental signals regulates stem cell functions. Bioengineering approaches, such as microtechnology tools, biomaterial fabrication, and computational methods coordinately enable the deconstruction of these complex microenvironments for systematic investigation, and the construction of engineered microenvironments for translational applications.

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Laboratory Methods and Technologies > Genetic/Genomic Methods
Models of Systems Properties and Processes > Cellular Models
Developmental Biology > Stem Cell Biology and Regeneration
Translational, Genomic, and Systems Medicine > Translational Medicine

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