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Effects of STI1 variation on phenotypic manifestation of different pluripotent status

Grant number: 20/05443-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2020
Effective date (End): August 31, 2021
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal researcher:Marilene Hohmuth Lopes
Grantee:Samuel Ribeiro Soares
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Pluripotent stem cells (PSCs), among them as embryonic stem cells(ESCs), have differentiation capacity in all adult somatic lines withoutsenescence, a characteristic known as pluripotency. Pluripotent status is transient inbut can be maintained in vitro by culturing cells in thepathways that regulate differentiation processes, including a leukemia molecule inhibiting factor(LIF). Several authors in the field of research in PSCs have discussed different differencespluripotency stages, some are already well defined, such as naive and primed, and statestransitory, such as the formative. Understanding the molecular mechanisms that regulatethese different stages / pluripotency status contribute to the understanding ofprocesses associated with maintaining indifference to ESCs and acquiring adifferentiated phenotype by cells, leading to progress and development heredity.Pluripotency is finely regulated at several levels, one of which isproteostasis network (PN), important for post-transcriptional control of transcription factors(TFs) fundamental to pluripotency. A PN is composed of proteins and shotguns, highlighting the performance of the HSP70, HSP90 heat shock proteins and their STI1 hardware, which allows the formation of a complex between two HSPs. Studiesrecently pointed out that TFs essential for maintaining pluripotency are customers ofmachines combined by HSP70-STI1-HSP90, but with specific relevance for that machineryfor maintaining pluripotency remains little known. STI1 is a constitutive protein evolutionarily conserved, whose deletion causes early lethality inmurine embryos, with few reaching the tenth day of intrauterine life, indicated toimportance of this protein in embryonic development.Despite the phenotype of unfeasibility, the molecular mechanisms regulated directly orindirectly by STI1, which leads to the unfeasibility, are still poorly understood.In addition, the STI1 function in maintaining pluripotency, either through ist rola as a co-chaperone or another not yet described role, also need to be investigated further. In this project, we aim to clarify a relationship between the modulation in the STI1 levels and theexpression of pluripotency markers of behavior variables (naive, formative and prepared),using mouse ESC (mESC) as a study model. Given theimportance of STI1 in embryonic development, we seek to understand whether the increase or decrease in the levels of this protein may impact the pluripotent of mESC.