Department of Medical and Biological Sciences, University of Udine, Udine, Italy.
PLoS One. 2012;7(7):e41774. doi: 10.1371/journal.pone.0041774. Epub 2012 Jul 23.
Although the role played by the core transcription factor network, which includes c-Myc, Klf4, Nanog, and Oct4, in the maintenance of embryonic stem cell (ES) pluripotency and in the reprogramming of adult cells is well established, its persistence and function in adult stem cells are still debated. To verify its persistence and clarify the role played by these molecules in adult stem cell function, we investigated the expression pattern of embryonic and adult stem cell markers in undifferentiated and fully differentiated dental pulp stem cells (DPSC). A particular attention was devoted to the expression pattern and intracellular localization of the stemness-associated isoform A of Oct4 (Oct4A). Our data demonstrate that: Oct4, Nanog, Klf4 and c-Myc are expressed in adult stem cells and, with the exception of c-Myc, they are significantly down-regulated following differentiation. Cell differentiation was also associated with a significant reduction in the fraction of DPSC expressing the stem cell markers CD10, CD29 and CD117. Moreover, a nuclear to cytoplasm shuttling of Oct4A was identified in differentiated cells, which was associated with Oct4A phosphorylation. The present study would highlight the importance of the post-translational modifications in DPSC stemness maintenance, by which stem cells balance self-renewal versus differentiation. Understanding and controlling these mechanisms may be of great importance for stemness maintenance and stem cells clinical use, as well as for cancer research.
虽然包括 c-Myc、Klf4、Nanog 和 Oct4 在内的核心转录因子网络在维持胚胎干细胞 (ES) 多能性和重编程成体细胞中的作用已得到充分证实，但它在成体干细胞中的持久性和功能仍存在争议。为了验证其持久性，并阐明这些分子在成体干细胞功能中的作用，我们研究了未分化和完全分化的牙髓干细胞 (DPSC) 中胚胎和成体干细胞标志物的表达模式。特别关注与 Oct4 相关的异构体 A（Oct4A）的表达模式和细胞内定位。我们的数据表明：Oct4、Nanog、Klf4 和 c-Myc 在成体干细胞中表达，并且除了 c-Myc 之外，它们在分化后显著下调。细胞分化也与表达干细胞标志物 CD10、CD29 和 CD117 的 DPSC 比例显著降低有关。此外，在分化细胞中鉴定到 Oct4A 的核质穿梭，其与 Oct4A 的磷酸化有关。本研究强调了翻译后修饰在 DPSC 干细胞维持中的重要性，通过这种修饰，干细胞在自我更新与分化之间保持平衡。理解和控制这些机制对于干细胞维持和干细胞的临床应用以及癌症研究可能非常重要。
