Department of Histology and Embryology, Harbin Medical University, Harbin, 150081, P. R. China.
Department of Histology and Embryology, Mudanjiang Medical University, Mudanjiang, 157011, P. R. China.
Sci Rep. 2018 Jul 19;8(1):10955. doi: 10.1038/s41598-018-29339-0.
Patient-specific induced pluripotent stem cells (iPSCs) have the potential to be useful in the treatment of human diseases. While prior studies have reported multiple methods to generate iPSCs, DNA methylation continues to limit the totipotency and reprogramming efficiency of iPSCs. Here, we first show the competency of embryonic germ cells (EGCs) as a reprogramming catalyst capable of effectively promoting reprogramming induced by four defined factors, including Oct4, Sox2, Klf4 and c-Myc. Combining EGC extracts with these four factors resulted in formation of more embryonic stem cell-like colonies than did factors alone. Notably, expression of imprinted genes was higher with combined induction than with factors alone. Moreover, iPSCs derived from the combined inductors tended to have more global hypomethylation. Our research not only provides evidence that EGC extracts could activate DNA demethylation and reprogram imprinted genes, but also establishes a new way to enhance reprogramming of iPSCs, which remains a critical safety concern for potential use of iPSCs in regenerative medicine.
患者特异性诱导多能干细胞（iPSCs）在人类疾病的治疗中有很大的应用潜力。虽然之前的研究已经报道了多种生成 iPSCs 的方法，但 DNA 甲基化仍然限制了 iPSCs 的全能性和重编程效率。在这里，我们首先展示了胚胎生殖细胞（EGCs）作为一种重编程催化剂的能力，它能够有效地促进由四个定义的因子（包括 Oct4、Sox2、Klf4 和 c-Myc）诱导的重编程。将 EGC 提取物与这四个因子结合使用，比单独使用这些因子形成更多的类胚胎干细胞集落。值得注意的是，与单独诱导相比，联合诱导的印迹基因表达更高。此外，来源于联合诱导物的 iPSCs 往往具有更多的全基因组低甲基化。我们的研究不仅提供了证据表明 EGC 提取物可以激活 DNA 去甲基化和重新编程印迹基因，而且还建立了一种增强 iPSCs 重编程的新方法，这对于 iPSCs 在再生医学中的潜在应用仍然是一个关键的安全问题。
