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Looking into the Black Box: Insights into the Mechanisms of Somatic Cell Reprogramming
Center for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave. B 119, Toronto, ON M5G 1X5, Canada
Department of Molecular Genetics, University of Toronto, Canada
* Author to whom correspondence should be addressed.
Received: 18 November 2010; in revised form: 22 December 2010 / Accepted: 5 January 2011 / Published: 13 January 2011
Abstract: The dramatic discovery that somatic cells could be reprogrammed to induced pluripotent stem cells (iPSCs), by the expression of just four factors, has opened new opportunities for regenerative medicine and novel ways of modeling human diseases. Extensive research over the short time since the first iPSCs were generated has yielded the ability to reprogram various cell types using a diverse range of methods. However the duration, efficiency, and safety of induced reprogramming have remained a persistent limitation to achieving a robust experimental and therapeutic system. The field has worked to resolve these issues through technological advances using non-integrative approaches, factor replacement or complementation with microRNA, shRNA and drugs. Despite these advances, the molecular mechanisms underlying the reprogramming process remain poorly understood. Recently, through the use of inducible secondary reprogramming systems, researchers have now accessed more rigorous mechanistic experiments to decipher this complex process. In this review we will discuss some of the major recent findings in reprogramming, pertaining to proliferation and cellular senescence, epigenetic and chromatin remodeling, and other complex cellular processes such as morphological changes and mesenchymal-to-epithelial transition. We will focus on the implications of this work in the construction of a mechanistic understanding of reprogramming and discuss unexplored areas in this rapidly expanding field.
Keywords: induced pluripotent stem cells; mechanism of reprogramming; iPS; BMP; Wnt; p53; epigenetic; MET; PKA; histone modifications
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MDPI and ACS Style
David, L.; Samavarchi-Tehrani, P.; Golipour, A.; Wrana, J.L. Looking into the Black Box: Insights into the Mechanisms of Somatic Cell Reprogramming. Genes 2011, 2, 81-106.
David L, Samavarchi-Tehrani P, Golipour A, Wrana JL. Looking into the Black Box: Insights into the Mechanisms of Somatic Cell Reprogramming. Genes. 2011; 2(1):81-106.
David, Laurent; Samavarchi-Tehrani, Payman; Golipour, Azadeh; Wrana, Jeffrey L. 2011. "Looking into the Black Box: Insights into the Mechanisms of Somatic Cell Reprogramming." Genes 2, no. 1: 81-106.