title: miR-125 potentiates early neural specification of human embryonic stem cells.
abstract: The role of microRNAs (miRNAs) as coordinators of stem cell fate has emerged over the last decade. We have used human embryonic stem cells to identify miRNAs involved in neural lineage commitment induced by the inhibition of TGFβ-like molecule-mediated pathways. Among several candidate miRNAs expressed in the fetal brain, the two isoforms of miR-125 alone were detected in a time window compatible with a role in neural commitment in vitro. Functional analysis indicated that miR-125 isoforms were actively involved in the promotion of pluripotent cell conversion into SOX1-positive neural precursors. miR-125 promotes neural conversion by avoiding the persistence of non-differentiated stem cells and repressing alternative fate choices. This was associated with the regulation by miR-125 of SMAD4, a key regulator of pluripotent stem cell lineage commitment. Activation of miR-125 was directly responsive to the levels of TGFβ-like molecules, placing miR-125 at the core of mechanisms that lead to the irreversible neural lineage commitment of pluripotent stem cells in response to external stimuli.
authors.affiliation: INSERM U861, AFM, Evry Cedex, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Boissart
authors.forename: Xavier
authors.initials: X
authors.lastname: Nissan
authors.forename: Karine
authors.initials: K
authors.lastname: Giraud-Triboult
authors.forename: Marc
authors.initials: M
authors.lastname: Peschanski
authors.forename: Alexandra
authors.initials: A
authors.lastname: Benchoua
mesh_terms: D028341:Activins / Q000378:metabolism; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002469:Cell Separation; D053595:Embryonic Stem Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology; D020033:Protein Isoforms; D051901:Smad4 Protein / Q000378:metabolism
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D020033:Protein Isoforms; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D028341:Activins