title: MRAS GTPase is a novel stemness marker that impacts mouse embryonic stem cell plasticity and Xenopus embryonic cell fate.
abstract: 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.
authors.affiliation: University of Bordeaux, CIRID, UMR 5164, F-33000 Bordeaux, France.
authors.forename: Marie-Emmanuelle
authors.initials: ME
authors.lastname: Mathieu
authors.forename: Corinne
authors.initials: C
authors.lastname: Faucheux
authors.forename: Claire
authors.initials: C
authors.lastname: Saucourt
authors.forename: Fabienne
authors.initials: F
authors.lastname: Soulet
authors.forename: Xavier
authors.initials: X
authors.lastname: Gauthereau
authors.forename: Sandrine
authors.initials: S
authors.lastname: Fédou
authors.forename: Marina
authors.initials: M
authors.lastname: Trouillas
authors.forename: Nadine
authors.initials: N
authors.lastname: Thézé
authors.forename: Pierre
authors.initials: P
authors.lastname: Thiébaud
authors.forename: Hélène
authors.initials: H
authors.lastname: Boeuf
mesh_terms: D028341:Activins / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000201:enzymology; D017124:Conserved Sequence; D004627:Embryonic Induction; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005775:Gastrula / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D055495:Neurogenesis; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000201:enzymology; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; D053605:Leukemia Inhibitory Factor; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D028341:Activins; D005346:Fibroblast Growth Factors; C109418:Mras protein, mouse; D020559:Monomeric GTP-Binding Proteins; D018631:ras Proteins
keywords: LIF; Mouse; Mras; Neurogenesis; Pluripotency; Xenopus; mES cells