Groucho related gene 5 (GRG5) is involved in embryonic and neural stem cell state decisions

Chanoumidou, KonstantinaSkåne University Hospital,Foundation for Research and Technology - Hellas,Democritus University of Thrace (author)

Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. By both loss and gain of function approaches we demonstrate that ablation of GRG5 deregulates the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. The malignant characteristics of teratomas generated by ESCs that overexpress GRG5 reveal its pro-oncogenic potential. Furthermore, transcriptomic analysis and cell differentiation approaches underline GRG5 as a multifaceted signaling regulator that represses mesendodermal-related genes. When ESCs exit pluripotency, GRG5 promotes neuroectodermal specification via Wnt and BMP signaling suppression. Moreover, GRG5 promotes the neuronal reprogramming of fibroblasts and maintains the self-renewal of Neural Stem Cells (NSCs) by sustaining the activity of Notch/Hes and Stat3 signaling pathways. In summary, our results demonstrate that GRG5 has pleiotropic roles in stem cell biology functioning as a stemness factor and a neural fate specifier.

Hadjimichael, ChristianaFoundation for Research and Technology - Hellas (author)
Athanasouli, ParaskeviFoundation for Research and Technology - Hellas,University of Crete (author)
Ahlenius, HenrikLund University,Lunds universitet,Stamceller, åldrande och neurodegeneration,Forskargrupper vid Lunds universitet,Stem Cells, Aging and Neurodegeneration,Lund University Research Groups,Skåne University Hospital(Swepub:lu)neur-hah (author)
Klonizakis, AntonisUniversity of Crete (author)
Nikolaou, ChristoforosUniversity of Crete (author)
Drakos, EliasUniversity of Crete (author)
Kostouros, AntonisUniversity of Crete (author)
Stratidaki, IreneFoundation for Research and Technology - Hellas (author)
Grigoriou, MariaDemocritus University of Thrace (author)
Kretsovali, AndronikiFoundation for Research and Technology - Hellas (author)
Skåne University HospitalFoundation for Research and Technology - Hellas (creator_code:org_t)

By the author/editor: Chanoumidou, Kon ...; Hadjimichael, Ch ...; Athanasouli, Par ...; Ahlenius, Henrik; Klonizakis, Anto ...; Nikolaou, Christ ...; show more...; Drakos, Elias; Kostouros, Anton ...; Stratidaki, Iren ...; Grigoriou, Maria; Kretsovali, Andr ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.