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

Chanoumidou, Konstantina ; Hadjimichael, Christiana ; Athanasouli, Paraskevi ; Ahlenius, Henrik LU ; Klonizakis, Antonis ; Nikolaou, Christoforos ; Drakos, Elias ; Kostouros, Antonis ; Stratidaki, Irene and Grigoriou, Maria , et al. (2018) In Scientific Reports 8(1).
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
8
issue
1
article number
13790
publisher
Nature Publishing Group
external identifiers
  • scopus:85053319841
  • pmid:30214018
ISSN
2045-2322
DOI
10.1038/s41598-018-31696-9
language
English
LU publication?
yes
id
cff68a89-6c2d-4c01-bb73-f703fae4c4f9
date added to LUP
2018-10-08 12:09:34
date last changed
2021-10-06 01:20:57
@article{cff68a89-6c2d-4c01-bb73-f703fae4c4f9,
  abstract     = {<p>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.</p>},
  author       = {Chanoumidou, Konstantina and Hadjimichael, Christiana and Athanasouli, Paraskevi and Ahlenius, Henrik and Klonizakis, Antonis and Nikolaou, Christoforos and Drakos, Elias and Kostouros, Antonis and Stratidaki, Irene and Grigoriou, Maria and Kretsovali, Androniki},
  issn         = {2045-2322},
  language     = {eng},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Groucho related gene 5 (GRG5) is involved in embryonic and neural stem cell state decisions},
  url          = {http://dx.doi.org/10.1038/s41598-018-31696-9},
  doi          = {10.1038/s41598-018-31696-9},
  volume       = {8},
  year         = {2018},
}