Bressan et al SBTE 2011 Reprogramming somatic cells trough gene induction and nuclear reprogramming (original) (raw)

The understanding of nuclear reprogramming pathways provides important contributions to applied and basic sciences such as the development of autologous cellular therapies for the treatment of numerous diseases, the improved efficiency of animal-based biotechnology or the generation of functional gametes in vitro. Strategies such as nuclear transfer and induced reprogramming have been used to induce somatic cells into an embryonic-like pluripotent state. Both techniques have been routinely performed worldwide, and live offspring have been successfully derived from them, resulting in a proof of efficacy of both techniques. Detailed studies on cellular and molecular mechanisms that mediate reprogramming, however, still require further investigation to develop practical applications in veterinary and human medicine. Review: Studies on cell reprogramming, differentiation and proliferation have revealed that a core of transcription factors, as for example, OCT4, SOX2 and NANOG, act together promoting cell commitment or pluripotency. Mechanisms of induced reprogramming by pluripotency-related transcription factors forced expression or nuclear transfer seems to be mediated by the same pathways observed in fertilization, eliciting nuclear remodeling and modulating gene expression. However, abnormal chromatin conformation, often leading to disrupted imprinting and atypical gene expression patterns are frequently observed on in vitro reprogramming. Strategies used to facilitate nuclear remodeling, such as chromatin modifying agents, as for example, histone deacetilases inhibitors or DNA methyltransferases; or chemicals responsible for the inhibition of developmentrelated pathways, as for example, MEK and GSK3 inhibitors, when used in the in vitro culture of cells or embryos, have proved to favors transcriptional regulation and improve reprogramming. Such alternatives are highly prone to enable the routine use of in vitro reprogramming in animal production and medical sciences, for example, by promoting the generation of functional male and female functional gametes capable of producing viable offspring. Thus, the properties, deficiencies and implications of induced reprogramming and nuclear transfer techniques in somatic cells were discussed in this review, as well as its probable outcomes.