Impact of co-chaperone STIP1 expression in the pluripotency acquision induced by Oct4 in murine fibroblasts

Abstract

Pluripotent cell have the potential to differentiate into all of the cell typesof an animal. This unique cell state is governed by an interconnected network of transcription factors, being Oct4 a central player in pluripotency induction and maintenance. Evidence pointed out to the participation of proteostase machinary regulated by co-chaperone STIP1 (Stress Inducible Phosphoprotein 1) and its partners, Hsp70 e Hsp90, in the embryogenesis and maintenance of pluripotent stem cells. Our data have revealed that STIP1 silencing impairs the pluripotent status of embryonic stem cells decreasing the expression of multiple transcription factors, including Oct4, Sox2, Nanog and STAT3. Interestingly, literature findings showed that Hsp90 is able to maintain stable the levels of pluripotency transcription factors, particularly, Oct4. Indeed, a depth study aimed the role of STIP1 and its partners in the regulation and maintenance of pluripotency is crucial to understanding the basic mechanisms that control stem cell pluripotency. Thus, the main goal of this proposal is to evaluate the role of STIP1 in the regulation of Oct4 expression in murine fibroblasts derived from transgenic mice expressing different STIP1 levels (wild-type, haploinsufficient and overexpressing STIP1) and a truncate isoform (deletion mutant for TPR1, the Hsp70 binding site) and consequently, to evaluate their participation in pluripotent state induction. Hence, dissecting the molecular basic of the stem cell pluripotency is essential to understand the biology of stem cells, the early embryonic developing and for clinical application in regenerative medicine. (AU)