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

• Grant number: 19/10367-5
• Support Opportunities: 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: Jennifer Nichols
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: 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 most mammals, where one of the two X chromosomes in females is silenced in order to achieve the same expression level of the only X present in males. This process takes place early in the development 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, although recently 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 model for the study of the X inactivation, enabling the development of new cell lines that, upon differentiation, reflect the human progression of the XCI. (AU)