miR-371-3 Expression Predicts Neural Differentiation Propensity in Human Pluripotent Stem Cells

• Published in: Cell stem cell 2011-06, Vol.8 (6), p.695-706
• Main Authors: Kim, Hyesoo, Lee, Gabsang, Ganat, Yosif, Papapetrou, Eirini P., Lipchina, Inna, Socci, Nicholas D., Sadelain, Michel, Studer, Lorenz
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Differentiation - genetics; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cells, Cultured; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Humans; Immunohistochemistry; MicroRNAs - genetics; Molecular and cellular biology; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2011.04.002

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. ► Differential expression of a range of markers among 39 hPSC lines ► miR-371-3 expression correlates negatively with neurogenic propensity ► KLF4 transduction induces miR-371-3 and inhibits neural differentiation ► miR-371-3 loss of function rescues KLF4-induced repression of neurogenic propensity