Deciphering the complexities of human diseases and disorders by coupling induced-pluripotent stem cells and systems genetics.

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.