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WIREs Syst Biol Med
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Deciphering the complexities of human diseases and disorders by coupling induced‐pluripotent stem cells and systems genetics

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Abstract The recent discovery that adult mouse and human somatic cells can be ‘reprogrammed’ to a state of pluripotency by ectopic expression of only a few transcription factors has already made a major impact on the biomedical community. For the first time, it is possible to study diseases on an individual patient basis, which may eventually lead to the realization of personalized medicine. The utility of induced‐pluripotent stem cells (iPSCs) for modeling human diseases has greatly benefitted from established human embryonic stem cell (ESC) differentiation and tissue engineering protocols developed to generate many different cell and tissue types. The limited access to preimplantation genetic tested embryos and the difficulty in gene targeting human ESCs have restricted the use of human ESCs in modeling human disease. Afforded by iPSC technology is the ability to study disease pathogenesis as it unfolds during tissue morphogenesis. The complexities of molecular signaling and interplay with protein transduction during disease progression necessitate a systems approach to studying human diseases, whereby data can be statistically integrated by sorting out the signal to noise issues that arise from global biological changes associated with disease versus experimental noise. Using a systems approach, biomarkers can be identified that define the initiation or progression of disease and likewise can serve as putative therapeutic targets. WIREs Syst Biol Med 2012 doi: 10.1002/wsbm.1170 This article is categorized under: Models of Systems Properties and Processes > Cellular Models Laboratory Methods and Technologies > Genetic/Genomic Methods Translational, Genomic, and Systems Medicine > Translational Medicine

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A representation showing the coupling of induced‐pluripotent stem cells (iPSCs) and systems genetics. iPSCs have been derived from numerous tissues, such as blood, which is an easily accessible source from patient cells. Once the iPSCs are generated and the appropriate cell lineage is derived such as neurons, systems methodologies can be used to interrogate gene and miRNA expression and combined with other systems approaches such as proteomics. The collection of these different systems level datasets can be computationally analyzed to yield higher order signaling networks. The ultimate goal is that this information will lead to a better understanding of human diseases and disorders and perhaps novel therapeutics.

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Models of Systems Properties and Processes > Cellular Models
Laboratory Methods and Technologies > Genetic/Genomic Methods
Translational, Genomic, and Systems Medicine > Translational Medicine

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