title: The RNA-binding protein Unr prevents mouse embryonic stem cells differentiation toward the primitive endoderm lineage.
abstract: The maintenance of embryonic stem cells (ESCs) pluripotency depends on key transcription factors, chromatin remodeling proteins, and microRNAs. The roles of RNA-binding proteins are however poorly understood. We report that the cytoplasmic RNA-binding protein Unr prevents the differentiation of ESCs into primitive endoderm (PrE). We show that unr knockout (unr(-/-) ) ESCs spontaneously differentiate into PrE, and that Unr re-expression in unr(-/-) ESCs reverses this phenotype. Nevertheless, unr(-/-) ESCs retain pluripotency, producing differentiated teratomas, and the differentiated unr(-/-) ESCs coexpress the PrE inducer Gata6 and the pluripotency factors Oct4, Nanog, and Sox2. Interestingly, in the differentiated unr(-/-) ESCs, Nanog and Sox2 exhibit a dual nuclear and cytoplasmic localization. This situation, that has never been reported, likely reflects an early differentiation state toward PrE. Finally, we show that Unr destabilizes Gata6 mRNAs and we propose that the post-transcriptional repression of Gata6 expression by Unr contributes to the stabilization of the ESCs pluripotent state.
authors.affiliation: Physiopathologie du Cancer du Foie, Université de Bordeaux, Physiopathologie du cancer du foie, U1053, Bordeaux, France.
authors.forename: Habiba
authors.initials: H
authors.lastname: Elatmani
authors.forename: Virginie
authors.initials: V
authors.lastname: Dormoy-Raclet
authors.forename: Pierre
authors.initials: P
authors.lastname: Dubus
authors.forename: François
authors.initials: F
authors.lastname: Dautry
authors.forename: Claire
authors.initials: C
authors.lastname: Chazaud
authors.forename: Hélène
authors.initials: H
authors.lastname: Jacquemin-Sablon
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D061252:Feeder Cells; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D055786:Gene Knockout Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013724:Teratoma / Q000473:pathology; D014162:Transfection
chemical_list: D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; D039102:Poly(A)-Binding Proteins; C494174:Pou5f1 protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C489441:UNR protein, mouse