Department of Biomedical Science, College of Life Science and CHA Stem Cell Institute, CHA University, 335, Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-400, Korea.
Stem Cell Res Ther. 2019 Jan 17;10(1):32. doi: 10.1186/s13287-019-1137-9.
Ell3 is a RNA polymerase II elongation factor that has various cell type-dependent functions, such as regulating the differentiation efficiency of embryonic stem cells and sensitizing cancer cells to anticancer drugs. However, there has been little research on the role of Ell3 on the regulation of senescence and apoptosis of stem cells.
We analyzed the senescence of Ell3-suppressed stem cells by mitochondrial activity, β-gal (+) cells, and lineage differentiation efficiency. The apoptosis of Ell3-overexpressing stem cells was analyzed by Annexin V staining, Immunoblot, and Live&dead assay. In addition, chromatin immunoprecipitation and luciferase assays were used to demonstrate p53 functions as a direct transcriptional activator of Ell3.
Suppression of Ell3 expression induced senescence in stem cells by increasing Bcl-2 expression. Unlike the effect of Ell3 suppression, the ectopic expression of Ell3 induces apoptosis of stem cells and induces apoptosis of adjacent cells. In addition, p53 functions as a direct transcriptional activator of Ell3 during the stem cell apoptosis.
We suggest that the function of Ell3 is associated with the p53-Bcl2 axis in both senescent and apoptotic ADSCs.
Ell3 是 RNA 聚合酶 II 延伸因子，具有多种细胞类型依赖性功能，例如调节胚胎干细胞的分化效率和使癌细胞对抗癌药物敏感。然而，关于 Ell3 对干细胞衰老和凋亡的调节作用的研究甚少。
我们通过线粒体活性、β-gal（+）细胞和谱系分化效率分析 Ell3 抑制的干细胞衰老。通过 Annexin V 染色、免疫印迹和 Live&Dead 测定分析 Ell3 过表达干细胞的凋亡。此外，还使用染色质免疫沉淀和荧光素酶测定来证明 p53 作为 Ell3 的直接转录激活因子的功能。
抑制 Ell3 表达通过增加 Bcl-2 表达诱导干细胞衰老。与 Ell3 抑制的作用不同，Ell3 的异位表达诱导干细胞凋亡，并诱导相邻细胞凋亡。此外，p53 在干细胞凋亡过程中作为 Ell3 的直接转录激活因子发挥作用。
我们表明 Ell3 的功能与 p53-Bcl2 轴在衰老和凋亡 ADSC 中都有关。
