Involvement of STI1 in the proliferation control of embryonic stem cells

• Grant number: 12/18466-3
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2012
• Effective date (End): June 30, 2013
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal researcher: Marilene Hohmuth Lopes
• Grantee: Angela Del Ry Menezes
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 11/13906-2 - Contribution of the co-chaperone STI1 in mouse development: embryonic stem cell as approach, AP.JP

Abstract

Stress inducible protein 1 is known as a co-chaperone capable of modulating the activity of heat shock proteins (Hsps) 70-90 kDa. Its cell distribution indicates that this protein can form multiprotein complexes in the nucleus, cytoplasm and extracellular milleu, with different biological activities. In their soluble form interacts with the cellular prion protein (PrPC), a plasma membrane glycoprotein with important functions in the developing nervous system and neural plasticity. Recently STI1 has been observed regulating the pluripotency status of embryonic stem cells and modulating self-renewal and proliferation of neural stem cells.To address whether STI1 plays a role in embryogenesis, a mouse deficient for STI1 gene was generated. An important finding was that the the deletion of STI1 gene in both alleles is lethal and leads to embryonic malformation which appears between the sixth and tenth day of murine development. It is noteworthy that the frequency of implantation and embryo development until the tenth day of intrauterine life is very low compared to the number of blastocysts STI1 knockout found. Thus, this molecule could be an indispensable factor in the development of mammals.Finally, culture of embryonic stem cells, it is the most appropriated approach to study the mechanism involved in the lethality of embryos deficient for STI1 in the initial period of development, being the only model that mimics the development of the epiblast In vitro with ability to contribute to all cells of fetal tissue, including the germ line.Given these data showing STI1 involved in the proliferation of neural stem cells, the main objective of this project is to evaluate the participation of STI1 in controlling proliferation of ESCs lines expressing different levels of STI1.