Mesenchymal stem cells (MSCs) derived from human embryonic stem cells (hESCs) have significant potential for cell-mediated bone regeneration. Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of hESCs. In this study, an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6 (GDF6), which is involved in bone formation, was the most upregulated gene associated with MSCs compared to hESCs. Furthermore, we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC population. Our results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine.

源自人胚胎干细胞 (hESC) 的间充质干细胞 (MSC) 在细胞介导的骨再生方面具有巨大潜力。我们最近的研究表明，抑制表观遗传调节因子 EZH2 在促进 hESC 中胚层分化中起着关键作用。在这项研究中，对 hESC 和 MSC 进行的全表观基因组分析表明，与 hESC 相比，参与骨形成的生长分化因子 6 (GDF6) 是与 MSC 相关的上调程度最高的基因。此外，我们将 GDF6 确定为 EZH2 的抑制靶点，并发现异位 GDF6 选择性促进 hESC 向中胚层谱系分化并丰富 MSC 群体。我们的结果提供了控制 hESC 间充质承诺的分子见解，并确定了一个为再生医学的未来带来光明希望的诱导因子。