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Impact of the depletion of the co-chaperone STI1 in the control of pluripotency, proliferation and differentiation of murine embryonic stem cells

Grant number: 14/17385-5
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): June 01, 2015
Effective date (End): December 05, 2016
Field of knowledge:Biological Sciences - Biology
Principal researcher:Marilene Hohmuth Lopes
Grantee:Jenny Andrea Arévalo Romero
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


STI1 (Stress Inducible Protein 1) was originally characterized as a co-chaperonin that interacts with heat shock proteins Hsp70 and Hsp90 and regulates its activity in the control of protein folding. However, recent studies demonstrate its broad functional versatility and show its mediation in neurotrophic effects in biological processes such as neuritogenesis, neuroprotection, development of astrocytes, self-renewal and proliferation of neural stem cells and memory consolidation, working with its primary ligand, Prion protein (PrPC). Interestingly, recent data show that STI1 depletion is lethal to mouse development. The absence of expression of STI1 directly affects early embryonic development. Deficient STI1 blastocysts (E 3.5) feature an atypical Mendelian frequency, with a low frequency of knockout STI1 embryos (13%) with apparently degeneration. Embryonic Stem Cells (ESCs) represent natural units of embryonic development and tissue regeneration. These cells have an unlimited capacity for self-renewal and potential to differentiate into any cell type of the body. Murine ESCs, CTEm, which were established such as permanent cell lines derived from blastocysts, can be considered a very versatile biological system and has led important advances in Cell Biology and development. Given these data, we use a CTEm cell line (ES-E14TG2a) as a study model. Therefore, the main objective of this study is to generate CTEm populations with different levels of STI1 expression to characterize the functions of this molecule in cell proliferation, pluripotency, differentiation and cell survival. Finally, the characterization of promising molecules and their functions lead a better understanding of the CTEm Biology and portend the therapeutic use of these cells in Regenerative Medicine. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CRUZ, LILIAN; ROMERO, JENNY A. A.; IGLESIA, REBECA P.; LOPES, MARILENE H. Extracellular Vesicles: Decoding a New Language for Cellular Communication in Early Embryonic Development. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 6, AUG 28 2018. Web of Science Citations: 8.
CRUZ, LILIAN; AREVALO ROMERO, JENNY ANDREA; PRADO, MARIANA BRANDAO; SANTOS, TIAGO G.; LOPES, MARILENE HOHMUTH. Evidence of Extracellular Vesicles Biogenesis and Release in Mouse Embryonic Stem Cells. STEM CELL REVIEWS AND REPORTS, v. 14, n. 2, p. 262-276, APR 2018. Web of Science Citations: 5.

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