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WIREs Syst Biol Med
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Stem cell genome‐to‐systems biology

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Abstract Stem cells are capable of extended proliferation and concomitantly differentiating into a plethora of specialized cell types that render them apropos for their usage as a form of regenerative medicine for cell replacement therapies. The molecular processes that underlie the ability for stem cells to self‐renew and differentiate have been intriguing, and elucidating the intricacies within the genome is pertinent to enhance our understanding of stem cells. Systems biology is emerging as a crucial field in the study of the sophisticated nature of stem cells, through the adoption of multidisciplinary approaches which couple high‐throughput experimental techniques with computational and mathematical analysis. This allows for the determination of the molecular constituents that govern stem cell characteristics and conjointly with functional validations via genetic perturbation and protein location binding analysis necessitate the construction of the complex transcriptional regulatory network. With the elucidation of protein–protein interaction, protein–DNA regulation, microRNA involvement as well as the epigenetic modifications, it is possible to comprehend the defining features of stem cells at the system level. WIREs Syst Biol Med 2012, 4:39–49. doi: 10.1002/wsbm.151 This article is categorized under: Developmental Biology > Stem Cell Biology and Regeneration

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Building the network model for pluripotent state of stem cells through the integration of mathematical and computational disciplines with high‐throughput experimental methodologies. With systems biology, different layers of the stem cells biology are explored. The molecular determinants of stem cells are defined, protein–protein interaction map, transcriptional regulatory network that is constructed through the analysis of both the transcriptome and location binding and the epigenetic status of stem cells.

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Understanding the genome from one‐dimensional, two‐dimensional, and three‐dimensional views. A single‐dimension level reveals the essential molecular elements (red) that are required to maintain the stemness of stem cells. Establishing functional interactions between/among the molecular elements reveals a two‐dimensional understanding of the genome. A three‐dimensional insight can be gained through the higher‐order organization of the genome.

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