Study of the Role of STIP1 in the Regulation of Proteostasis and Pluripotency in Human iPSCs

• Grant number: 24/21638-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2025
• End date: January 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marilene Hohmuth Lopes
• Grantee: Lucas Prestes Helzel
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/15557-4 - Prion protein and its partners: emerging targets for glioblastoma stem cell based-therapy, AP.JP2

Abstract

Stem cells have the ability to differentiate into various cell types and self-renew, being classified according to their level of specialization. Induced pluripotent stem cells (iPSCs) are pluripotent cells reprogrammed from adult somatic cells through the use of specific transcription factors. The control of pluripotency involves the coordinated function of various components, such as transcription factors, enzymes, and other proteins. Protein homeostasis, or proteostasis, ensures the proper production, folding, and maintenance of proteins within cells. This process is highly relevant in the context of pluripotency due to the high translation rates and precise regulation of molecular mechanisms for self-renewal and differentiation. The stress-inducible phosphoprotein 1 (STIP1) is involved in maintaining proteostasis, as well as in cell viability and metabolism, being part of the HSP70 and HSP90 chaperone complex. Studies indicate that regular levels of STIP1 are associated with the maintenance of critical processes for pluripotency, and its dysfunction may lead to impairments in embryonic development and the biology of pluripotent cells. Reduced levels of STIP1 have been linked to increased DNA damage and apoptosis, and its deletion is lethal to mouse embryonic development. Studying STIP1 in human iPSCs may help elucidate the molecular mechanisms and pathways related to the maintenance of pluripotency, differentiation potential, and protein regulation in these cells. Despite the promising insights, studies on the STIP1 protein remain scarce, and further research is needed to better understand its significance in the biology of pluripotent cells. Therefore, the main objective of this work is to evaluate the impact of STIP1 expression on the pluripotency and proteostasis mechanisms of iPSCs using a lentiviral system and overexpression vectors. Functional assays including cell viability and proteasome activity will be conducted, as well as the assessment of the pluripotency factors expression. Our results may contribute to the development of future cell therapies and a better understanding of stem cell function.