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Status |
Public on Dec 25, 2018 |
Title |
Groucho related gene 5 (GRG5) is required for the maintenance of embryonic and neural stem cells |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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. A pro-oncogenic potential for GRG5 is revealed by the malignant behavior of teratomas generated from ESCs that overexpress it. Furthermore, transcriptomic analysis and cell differentiation approaches underline GRG5 as a multifaceted signaling regulator that represses mesendodermal-related genes. When ES cells exit pluripotency, GRG5 promotes neuroectodermal specification via Wnt and BMP signaling pathways suppression. Moreover, GRG5 promotes the neuronal reprogramming of fibroblasts and maintains the self-renewal of Neural Stem Cell (NSC) by sustaining the activity of Notch and Jak/Stat3 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.
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Overall design |
Gene expression profiling of control and Grg5 knockdown (KD) embryonic stem cells with RNA-seq, in dublicate, using Ion Torrent Proton.
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Contributor(s) |
Chanoumidou K, Hadjimichael C, Ahlenius H, Nikolaou C, Klonizakis A, Drakos E, Kostouros A, Grigoriou M, Kretsovali A |
Citation(s) |
30214018 |
Submission date |
Nov 17, 2017 |
Last update date |
May 15, 2019 |
Contact name |
KONSTANTINA CHANOUMIDOU |
E-mail(s) |
k.chanoumidou@gmail.com
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Organization name |
Foundation for research and technology - HELLAS (FORTH)
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Department |
Institute of Molecular Biology and Biotechnology (IMBB)
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Lab |
Development and gene expression (A. Kretsovali laboratory)
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Street address |
Nikolaou Plastira 100
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City |
Heraklion, Crete |
ZIP/Postal code |
GR70013 |
Country |
Greece |
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Platforms (1) |
GPL18635 |
Ion Torrent Proton (Mus musculus) |
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Samples (4)
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Relations |
BioProject |
PRJNA418951 |
SRA |
SRP125202 |