Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York 10065, USA.
Genes Dev. 2011 Oct 15;25(20):2173-86. doi: 10.1101/gad.17221311.
MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understood, partially due to the lack of genome-wide strategies to identify their targets. Here, we performed comprehensive microRNA profiling in hESCs and in purified neural and mesenchymal derivatives. Using a combination of AGO cross-linking and microRNA perturbation experiments, together with computational prediction, we identified the targets of the miR-302/367 cluster, the most abundant microRNAs in hESCs. Functional studies identified novel roles of miR-302/367 in maintaining pluripotency and regulating hESC differentiation. We show that in addition to its role in TGF-β signaling, miR-302/367 promotes bone morphogenetic protein (BMP) signaling by targeting BMP inhibitors TOB2, DAZAP2, and SLAIN1. This study broadens our understanding of microRNA function in hESCs and is a valuable resource for future studies in this area.
微小 RNA 是许多细胞过程中的重要调节因子，包括干细胞自我更新。最近的研究表明，它们作为多能性因子发挥作用，具有体细胞重编程的能力。然而，它们在人类胚胎干细胞（hESC）中的作用仍知之甚少，部分原因是缺乏全基因组策略来识别它们的靶标。在这里，我们在 hESC 中和纯化的神经和间充质衍生物中进行了全面的 microRNA 分析。我们使用 AGO 交联和 microRNA 扰动实验的组合，以及计算预测，鉴定了 miR-302/367 簇的靶标，这是 hESC 中最丰富的 microRNA。功能研究鉴定了 miR-302/367 在维持多能性和调节 hESC 分化中的新作用。我们表明，miR-302/367 除了在 TGF-β 信号通路中的作用外，还通过靶向 BMP 抑制剂 TOB2、DAZAP2 和 SLAIN1 促进骨形态发生蛋白（BMP）信号通路。这项研究拓宽了我们对 hESC 中 microRNA 功能的理解，并且是该领域未来研究的宝贵资源。
