Department of Life Science, National Chung Cheng University, Chia-Yi 621, Taiwan.
Adv Exp Med Biol. 2013;754:195-211. doi: 10.1007/978-1-4419-9967-2_10.
Mesenchymal stem cells (MSCs) are multipotent stem cells of mesodermal origin that can be isolated from various sources and induced into different cell types. Although MSCs possess immune privilege and are more easily obtained than embryonic stem cells, their propensity to tumorigenesis has not been fully explored. Epigenomic changes in DNA methylation and chromatin structure have been hypothesized to be critical in the determination of lineage-specific differentiation and tumorigenesis of MSCs, but this has not been formally proven. We applied a targeted DNA methylation method to methylate a Polycomb group protein-governed gene, Trip10, in MSCs, which accelerated the cell fate determination of MSCs. In addition, targeted methylation of HIC1 and RassF1A, both tumor suppressor genes, transformed MSCs into tumor stem cell-like cells. This new method will allow better control of the differentiation of MSCs and their use in downstream applications.
间充质干细胞（MSCs）是中胚层来源的多能干细胞，可从多种来源分离，并诱导为不同的细胞类型。虽然 MSCs 具有免疫特权，并且比胚胎干细胞更容易获得，但它们的致瘤性尚未得到充分研究。DNA 甲基化和染色质结构的表观基因组变化被认为在决定 MSCs 的谱系特异性分化和致瘤性方面至关重要，但这尚未得到正式证明。我们应用靶向 DNA 甲基化方法在 MSCs 中甲基化 Polycomb 组蛋白调控的基因 Trip10，这加速了 MSCs 的细胞命运决定。此外，靶向甲基化两个肿瘤抑制基因 HIC1 和 RassF1A，将 MSCs 转化为肿瘤干细胞样细胞。这种新方法将允许更好地控制 MSCs 的分化及其在下游应用中的使用。
