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Identifier 000421101
Title Exploring the role of Groucho-related gene 5 (Grg5) in self-renewal and neuronal differentiation of embryonic stem cells
Alternative Title Διερεύνηση του ρόλου της πρωτεΐνης Groucho-related gene 5 (Grg5) στην αυτο-ανανέωση και την νευρική διαφοροποίηση των εμβρυικών βλαστοκυττάρων
Author Αθανασούλη, Παρασκευή Π.
Thesis advisor Κρετσοβάλη, Ανδρονίκη
Abstract ESCs are characterized by two important properties: self-renewal and pluripotency. Deciphering the molecular mechanisms that regulate these two processes is a continuing inquiry appealing the interest of stem cell research. The identification of new factors as essential regulators contributes to the interpretation of ESC biology. Among other pathways, specific interest has been focused on the underlying mechanisms that govern ESC neural differentiation since their unraveling can permit the study of CNS development in vitro and help regenerative neurogenesis. Groucho Related Gene 5 (GRG5) is a truncated member of the murine Groucho family. GRG5 was initially characterized as antagonist of the co-repressive activity of the other family members (long GRGs), hence acting as a “de-repressor”. However, later studies have shown that it is a multifunctional protein with important role in diverse cellular processes and postnatal developmental procedures. Grg5 has been reported as a direct target of STAT3 in ESCs; however its role has not been elucidated yet. This study unveils GRG5 function as a critical component of the regulatory network of ESC pluripotency and its involvement in ESC differentiation. Loss and gain of function approaches demonstrate that GRG5 acts as a self-renewal promoting factor in ESCs by positively regulating the expression of pluripotency factors. Consequently, depletion of GRG5 deregulates the ESCs pluripotent state whereas its forced expression enhances ESC self-renewal. Interestingly, OE GRG5 ESCs exhibit cancer cell-like properties, implying also the implication of GRG5 in tumorigenicity. Moreover, we delineate GRG5 involvement especially in ESC neuroectodermal commitment via Wnt and BMP signaling suppression, pathways that are known to inhibit ESC neural specification. Specifically, we present for the first time the physical association of crucial mediators of these pathways with GRG5 unraveling the molecular mechanism of the observed phenomenon and thus tracing its executive role in neural fate determination.
Language English
Subject GRG5
Neural differentiation
Εμβρυικά βλαστοκύτταρα
Issue date 2019-07-26
Collection   Faculty/Department--Faculty of Sciences and Engineering--Department of Biology--Post-graduate theses
  Type of Work--Post-graduate theses
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