生长分化因子6是EZH2的一个抑制靶点，可促进人胚胎干细胞向间充质干细胞的定向分化。
Growth differentiation factor 6, a repressive target of EZH2, promotes the commitment of human embryonic stem cells to mesenchymal stem cells.
作者信息
Deng Pend, Yu Yongxin, Hong Christine, Wang Cun-Yu
机构信息
Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Section of Orthodontics, Division of Growth and Development, School of Dentistry, University of California Los Angeles, Los Angeles, CA, 90095, USA.
出版信息
Bone Res. 2020 Nov 17;8(1):39. doi: 10.1038/s41413-020-00116-y.
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.
源自人类胚胎干细胞（hESCs）的间充质干细胞（MSCs）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hESCs向中胚层分化中起关键作用。在本研究中，对hESCs和MSCs进行的全表观基因组分析显示，参与骨形成的生长分化因子6（GDF6）是与MSCs相比hESCs中上调最显著的基因。此外，我们确定GDF6是EZH2的抑制靶点，并发现异位表达的GDF6选择性地促进hESCs向中胚层谱系分化并富集MSC群体。我们的结果提供了关于hESCs间充质定向分化的分子见解，并确定了一种诱导因子，为再生医学的未来带来了巨大希望。
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