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Evaluation of pluripotency and self-renewal of murine embryonic stem cells with differential expression of STI1

Grant number: 19/06971-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2019
Effective date (End): July 31, 2020
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Marilene Hohmuth Lopes
Grantee:Maria Clara da Silva Souza
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Stress Inducible Protein 1 (STI1) is a protein constitutively expressed in differentorganisms since the earliest stages of embryonic development. Among the importantbiological roles played by STI1, its performance as cochaperone, forming a complexbetween the Hsp70-Hsp90 heat shock proteins, is of particular importance, helping inthe activity of these chaperones through the hydrolysis of ATP. Besides that, studiespoint out that STI1 is involved in a number of other important cellular processes. Theimportance of STI1 in the mammalian development is evidenced in experimentsperformed with knockout (total absence of the protein) mice, which were non-viable, with early degeneration of the embryo after the tenth day of intrauterine life (E10.5). One of the major study models used to reproduce embryonic development in mammals is murine embryonic stem cells (mESCs). The ability of these cells to replicate indefinitely without death requires an increase in chaperones and cochaperones proteins. Given the importance of STI1 in the embryonic development, the mainobjective of this work is to analyze the relevance of this protein in the proliferation and maintenance of pluripotency of ESCs in the face of its loss-of-function, by comparingthe proliferation and differentiation of cells expressing different levels of STI1, withwild-type cells. Thus, our study will contributes to the understanding of the importance of STI1 in the biology of ESC, and may reveal new molecular mechanisms involved inthe pluripotency status of these cells.