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

Scientific Reports
Konstantina ChanoumidouAndroniki Kretsovali

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 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 neu...Continue Reading

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Citations

Dec 9, 2020·Development, Growth & Differentiation·Noriaki SasaiAgnes Ong Lee Chen

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Methods Mentioned

BETA
Profiler
Co-immunoprecipitation assay
RNA-seq
co-immunoprecipitation
transfection
immunoprecipitation
mechanical dissociation

Software Mentioned

DeSeq
Galaxy
Trimmomatic
FASTQC
STAR ( Spliced Transcripts Alignnment to a Reference )
Profiler
custom Perl script
: Profiler
FeatureCounts

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