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Derivation of naive stem cells for the characterization of the X chromosome inactivation

Grant number: 19/10367-5
Support type:Scholarships abroad - Research Internship - Master's degree
Effective date (Start): September 01, 2019
Effective date (End): February 29, 2020
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Lygia da Veiga Pereira
Grantee:Ana Luíza Cidral
Supervisor abroad: Jennifer Nichols
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University of Cambridge, England  
Associated to the scholarship:18/14856-8 - A study of the chromosome X inactivation in non-human primates, BP.MS

Abstract

The X chromosome inactivation is the dosage compensation mechanism present in mostmammals, where one of the two X chromosomes in females is silenced in order to achieve thesame expression level of the only X present in males. This process takes place early in thedevelopment and most of what is currently known about it originates from studies with mice.The embryonic nature of this mechanism restricts its experimental study in humans, althoughrecently some in silico analyses have been performed. This has helped scientists gain a better knowledge about the X inactivation, but still with limitations to be overcome. Other recent advances in studies with stem cells provided the scientific community with a novel type of stem cells called naïve, in respect to a state of pluripotency that differs from the conventional human stem cells, such as embryonic (hESCs) or induced pluripotency stem cells (iPSCs). Naïve stem cells, in comparison to primed cells, possess features that resemble the pluripotent cells in vivo, which also means that they carry two active X chromosome, while conventional primed cells have already undergone XCI and are in a later stage of development. The proposed derivation of naïve stem cells in this project, therefore, aims to generate a new modelfor the study of the X inactivation, enabling the development of new cell lines that, upondifferentiation, reflect the human progression of the XCI.