Toward Stem Cell Systems Biology: From Molecules toNetworks and Landscapes

摘要

The last few years have seen significant advances in our understanding of the molecular mechanisms of stem-cell-fate specifi-cation. New and emerging high-throughput techniques, as well as increasingly accurate loss-of-function perturbation techniques,are allowing us to dissect the interplay among genetic, epigenetic, proteomic, and signaling mechanisms in stem-cell-fate deter-mination with ever-increasing fidelity (Boyer ct al. 2005, 2006; Ivanova et al. 2006; Loh et al. 2006; Cole et al. 2008; Jiang etal. 2008; Johnson et al. 2008; Kim et al. 2008; Liu et al. 2008; Marson et al. 2008; Mathur et al. 2008). Taken together, recentreports using these new techniques demonstrate that stem-cell-fate specification is an extremely complex process, regulated bymultiple mutually interacting molecular mechanisms involving multiple regulatory feedback loops. Given this complexity andthe sensitive dependence of stem cell differentiation on signaling cues from the extracellular environment, how are we best todevelop a coherent quantitative understanding of stem cell fate at the systems level? One approach that we and other researchershave begun to investigate is the application of techniques derived in the computational disciplines (mathematics, physics, com-puter science, etc.) to problems in stem cell biology. Here, we briefly sketch a few pertinent results from the literature in this areaand discuss future potential applications of computational techniques to stem cell systems biology.