德国马克斯·普朗克分子生物医学研究所Hans R. Schöler和吴光明研究团队，揭示了Oct4非依赖诱导多能干细胞。 相关论文2019年11月7日发表在《细胞—干细胞》上。

研究人员发现Sox2、Klf4和cMyc(SKM)的组合，足以诱导小鼠体细胞重编程为诱导性多能干细胞(iPSCs)。在成纤维细胞中同时诱导表达Sox2和cMyc会立刻引起逆转录病毒沉默，这解释了之前使用逆转录病毒载体在表达没有Oct4的情况下却不能产生iPSC的原因。即使在Oct4基因敲除的成纤维细胞中，SKM诱导也可以部分激活多能网络。重要的是，通过测定iPSC在四倍体互补中产生iPSC小鼠的能力，研究人员发现在没有外源Oct4的情况下进行重编程，可大大提高iPSC的发育潜力。研究人员揭示了重编程过程中Oct4的过表达，可以激活重编程过程中的脱靶基因，还可以导致iPSC发生表观遗传畸变。这些都会对iPSC技术的进一步开发和应用产生影响。

研究人员表示，在四个Yamanaka重编程转录因子中，Oct4被认为是最重要的。

附：英文原文

Title: Excluding Oct4 from Yamanaka Cocktail Unleashes the Developmental Potential of iPSCs

Author: Sergiy Velychko, Kenjiro Adachi, Kee-Pyo Kim, Yanlin Hou, Caitlin M. MacCarthy, Guangming Wu, Hans R. Schler

Issue&Volume: November 07, 2019

Abstract: Oct4 is widely considered the most important among the four Yamanaka reprogramming factors. Here, we show that the combination of Sox2, Klf4, and cMyc (SKM) suffices for reprogramming mouse somatic cells to induced pluripotent stem cells (iPSCs). Simultaneous induction of Sox2 and cMyc in fibroblasts triggers immediate retroviral silencing, which explains the discrepancy with previous studies that attempted but failed to generate iPSCs without Oct4 using retroviral vectors. SKM induction could partially activate the pluripotency network, even in Oct4-knockout fibroblasts. Importantly, reprogramming in the absence of exogenous Oct4 results in greatly improved developmental potential of iPSCs, determined by their ability to give rise to all-iPSC mice in the tetraploid complementation assay. Our data suggest that overexpression of Oct4 during reprogramming leads to off-target gene activation during reprogramming and epigenetic aberrations in resulting iPSCs and thereby bear major implications for further development and application of iPSC technology.

DOI: 10.1016/j.stem.2019.10.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30423-0