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

Abstract

Stress Inducible Protein 1 (STI1) is a protein constitutively expressed in different organisms since the earliest stages of embryonic development. Among the important biological roles played by STI1, its performance as cochaperone, forming a complex between the Hsp70-Hsp90 heat shock proteins, is of particular importance, helping in the activity of these chaperones through the hydrolysis of ATP. Besides that, studies point out that STI1 is involved in a number of other important cellular processes. The importance of STI1 in mammalian development is evidenced in experiments performed 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 main objective 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 comparing the proliferation and differentiation of cells expressing different levels of STI1, with wild-type cells. Thus, our study will contribute to the understanding of the importance of STI1 in the biology of ESC, and may reveal new molecular mechanisms involved in the pluripotency status of these cells.