title: miR-371-3 expression predicts neural differentiation propensity in human pluripotent stem cells.
abstract: The use of pluripotent stem cells in regenerative medicine and disease modeling is complicated by the variation in differentiation properties between lines. In this study, we characterized 13 human embryonic stem cell (hESC) and 26 human induced pluripotent stem cell (hiPSC) lines to identify markers that predict neural differentiation behavior. At a general level, markers previously known to distinguish mouse ESCs from epiblast stem cells (EPI-SCs) correlated with neural differentiation behavior. More specifically, quantitative analysis of miR-371-3 expression prospectively identified hESC and hiPSC lines with differential neurogenic differentiation propensity and in vivo dopamine neuron engraftment potential. Transient KLF4 transduction increased miR-371-3 expression and altered neurogenic behavior and pluripotency marker expression. Conversely, suppression of miR-371-3 expression in KLF4-transduced cells rescued neural differentiation propensity. miR-371-3 expression level therefore appears to have both a predictive and a functional role in determining human pluripotent stem cell neurogenic differentiation behavior.
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
authors.forename: Hyesoo
authors.initials: H
authors.lastname: Kim
authors.forename: Gabsang
authors.initials: G
authors.lastname: Lee
authors.forename: Yosif
authors.initials: Y
authors.lastname: Ganat
authors.forename: Eirini P
authors.initials: EP
authors.lastname: Papapetrou
authors.forename: Inna
authors.initials: I
authors.lastname: Lipchina
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Socci
authors.forename: Michel
authors.initials: M
authors.lastname: Sadelain
authors.forename: Lorenz
authors.initials: L
authors.lastname: Studer
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D000090062:Kruppel-Like Factor 4; D035683:MicroRNAs / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C554834:MIRN371 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger