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Contribution of the co-chaperone STI1 in mouse development: embryonic stem cell as approach

Grant number: 11/13906-2
Support type:Research Grants - Young Investigators Grants
Duration: July 01, 2012 - June 30, 2016
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Marilene Hohmuth Lopes
Grantee:Marilene Hohmuth Lopes
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Tiago Góss dos Santos ; Vilma Regina Martins
Associated grant(s):18/15557-4 - Prion protein and its partners: emerging targets for glioblastoma stem cell based-therapy, AP.JP2
Associated scholarship(s):15/22147-9 - Study of STI1 function secreted during neuronal differentiation of murine embryonic stem cells, BP.IC
14/17385-5 - Impact of the depletion of the co-chaperone STI1 in the control of pluripotency, proliferation and differentiation of murine embryonic stem cells, BP.DD
13/23784-7 - Role of STI1 in embryonic stem cells proliferation, BP.IC
+ associated scholarships 12/21848-5 - Evaluate the expression of pluripontecy markers on embrionic stem cells lineages expressing different levels of STI1 protein, BP.IC
12/15014-4 - Functional study of the co-chaperone STI1 in murine embryonic stem cell biology, BP.MS
12/18466-3 - Involvement of STI1 in the proliferation control of embryonic stem cells, BP.IC - associated scholarships


Stress inducible protein 1 was originally identified as a co-chaperone able to modulate heat shock protein (Hsp) activities. In fact, several evidence suggest that STI1 is not only an adapter protein to link Hsps. The interaction of STI1 with various partners such as Hsp family members, transcription factors, prion protein (PrPC) among others, demonstrates its functional versatility. Several cellular localization of STI1 indicate that this protein could participate in the formation of multiprotein complexes in the nucleus, cytoplasm and/or extracellular milieu, with distinct biological activities. Interestingly, when at the extracellular space, the soluble form of STI1 is able to interact with PrPC, a cell surface glycoprotein, and orchestrates relevant biological phenomena related to nervous system development and neural plasticity, such as self-renewal of neural progenitors, control of neural differentiation and survival, and memory consolidation. Recent findings show STI1 involved in the regulation of pluripotency status of embryonic stem cells, suggesting a role for STI1 during embryogenesis. Given those data that demonstrate several biological functions associated to STI1, and in attempt to explore the role of STI1 in mammalian development, a constitutive knockout mouse, deficient for STI1 gene, was generated. Preliminary data show that in homozygous knockout animals, the STI1 deletion is lethal and leads to embryo degeneration which seems to occur between E6.5 and E10.5, indicating that STI1 could play an essential role during mammalian development. Hence, the culture of pluripotent embryonic stem cells, become an approach more adequate to study the mechanism involved in the lethality observed in STI1 knockout embryos during early development. Regarding that little is known about the contribution of STI1 to maintenance of embryonic stem cells and embryo development, and based on literature data that show the key role for STI1 in events that govern the brain plasticity during the development, the main goal of this proposal is to investigate the role of STI1 in the embryo development using embryonic stem cell as a model and evaluate the role of its main partner, PrPC, in these processes. (AU)

Scientific publications (4)
(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.
IGLESIA, REBECA PIATNICZKA; PRADO, MARIANA BRANDAO; CRUZ, LILIAN; MARTINS, VILMA REGINA; SANTOS, TIAGO GOSS; LOPES, MARILENE HOHMUTH. Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells. STEM CELL RESEARCH & THERAPY, v. 8, APR 17 2017. Web of Science Citations: 5.
SANTOS, TIAGO G.; LOPES, MARILENE H.; MARTINS, VILMA R. Targeting prion protein interactions in cancer. PRION, v. 9, n. 3, p. 165-173, MAY 4 2015. Web of Science Citations: 14.

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