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Development August 1, 2013; 140 (16): 3311-22.

MRAS GTPase is a novel stemness marker that impacts mouse embryonic stem cell plasticity and Xenopus embryonic cell fate.

Mathieu ME , Faucheux C , Saucourt C , Soulet F , Gauthereau X , Fédou S , Trouillas M , Thézé N , Thiébaud P , Boeuf H .

Pluripotent mouse embryonic stem cells (mESCs), maintained in the presence of the leukemia inhibitory factor (LIF) cytokine, provide a powerful model with which to study pluripotency and differentiation programs. Extensive microarray studies on cultured cells have led to the identification of three LIF signatures. Here we focus on muscle ras oncogene homolog (MRAS), which is a small GTPase of the Ras family encoded within the Pluri gene cluster. To characterise the effects of Mras on cell pluripotency and differentiation, we used gain- and loss-of-function strategies in mESCs and in the Xenopus laevis embryo, in which Mras gene structure and protein sequence are conserved. We show that persistent knockdown of Mras in mESCs reduces expression of specific master genes and that MRAS plays a crucial role in the downregulation of OCT4 and NANOG protein levels upon differentiation. In Xenopus, we demonstrate the potential of Mras to modulate cell fate at early steps of development and during neurogenesis. Overexpression of Mras allows gastrula cells to retain responsiveness to fibroblast growth factor (FGF) and activin. Collectively, these results highlight novel conserved and pleiotropic effects of MRAS in stem cells and early steps of development.

PubMed ID: 23863483
Article link: Development

Species referenced: Xenopus laevis
Genes referenced: cdx4 chrd.1 elavl3 esr-5 fgf2 gdf1 isl1 lif mras ncam1 neurog1 nog odc1 pak3 pnp pou5f3.1 runx1 smarca4 sox17a sox2 sult2a1 tbxt tub tubb2b wnt8a zfand4
Antibodies: Somite Ab1

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