Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10065, USA.
Cell Stem Cell. 2011 Jun 3;8(6):695-706. 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.
多能干细胞在再生医学和疾病建模中的应用受到细胞系间分化特性差异的影响。在这项研究中，我们对 13 个人胚胎干细胞（hESC）和 26 个人诱导多能干细胞（hiPSC）系进行了特征描述，以确定预测神经分化行为的标记物。在一般水平上，先前已知可区分小鼠胚胎干细胞（mESC）和外胚层干细胞（EPI-SCs）的标记物与神经分化行为相关。更具体地说，miR-371-3 的定量分析前瞻性地鉴定了具有不同神经发生分化倾向和体内多巴胺神经元植入潜力的 hESC 和 hiPSC 系。瞬时 KLF4 转导增加了 miR-371-3 的表达，并改变了神经发生行为和多能性标记物的表达。相反，在 KLF4 转导细胞中抑制 miR-371-3 的表达挽救了神经分化倾向。因此，miR-371-3 的表达水平似乎在决定人类多能干细胞神经发生分化行为方面具有预测和功能作用。
