miR-371-3 Expression Predicts Neural Differentiation Propensity in Human Pluripotent Stem Cells
miR-371-3 Expression Predicts Neural Differentiation Propensity in Human Pluripotent Stem Cells
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DOI：
10.1016/j.stem.2011.04.002
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发表时间：
2011-06-03
期刊：
影响因子：
23.9
通讯作者：
Studer, Lorenz
中科院分区：
文献类型：
--
作者：
Kim, Hyesoo;Lee, Gabsang;Studer, Lorenz
多能干细胞在再生医学和疾病建模中的应用由于细胞系之间分化特性的变化而变得复杂。在这项研究中，我们表征了13个人胚胎干细胞（hESC）和26个人诱导多能干细胞（hiPSC）系，以确定预测神经分化行为的标志物。在一般水平上，以前已知的区分小鼠胚胎干细胞和外胚层干细胞（EPI-SC）的标记物与神经分化行为相关。更具体地，miR-371-3表达的定量分析前瞻性地鉴定了具有不同神经源性分化倾向和体内多巴胺神经元移植潜力的hESC和hiPSC系。瞬时KLF 4转导增加了miR-371-3表达，改变了神经原性行为和多能性标志物表达。相反，在KLF 4转导的细胞中抑制miR-371-3表达拯救了神经分化倾向。因此，miR-371-3表达水平似乎在确定人多能干细胞神经源性分化行为中具有预测和功能作用。
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.