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Effect of induced pluripotency reprogramming on genomic imprinting maintenance

Grant number: 15/01407-2
Support type:Scholarships in Brazil - Master
Effective date (Start): June 01, 2015
Effective date (End): November 30, 2016
Field of knowledge:Agronomical Sciences - Veterinary Medicine
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Fabiana Fernandes Bressan
Grantee:Camila Martins Borges
Home Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil

Abstract

Reproductive biotechniques such as in vitro embryo production and somatic cell nuclear transfer may greatly contribute for fertility improvements, to enhance animal production or else to contribute to a better understanding of the underlying mechanism involved during initial embryonic development. However, in vitro manipulation of gametes or embryos may lead to possible disruptions on epigenetic regulation, causing high developmental abnormalities and decreased healthy calves born at term. The generation of the induced pluripotency models (induced pluripotent stem cells, or iPS) allowed studying the process of in vitro reprogramming in more a solid and precise manner. OCT4 and SOX2 are fundamental genes for the acquisition and maintenance process of cellular pluripotency. Recently, it has been reported that both factors may have a huge influence on the regulation of some imprinted genes, especially at locus H19/IGF2, known to be important for the normal development of embryo and placenta. It is hypothesized that OCT4 and SOX2 transcription factors may act in order to protect the imprinted locus IGF2/H19 against a possible hypermethylation due to the process of cellular reprogramming. Therefore, this study aims to generate an experimental model where the above transcription factors will be studied together or separately regarding their influence on genomic imprinting regulation. It is expected that the results obtained herein may contribute to enhance the efficiency of reproductive biotechnologies, resulting in the increased success on cellular reprograming, therefore also generating new tools for both regenerative and translational medicine. (AU)