Yuan Xia, Zhang Chen, Zhao Ruifeng, Jiang Jingyi, Shi Xiang, Zhang Ming, Sun Hongyan, Zuo Qisheng, Zhang Yani, Song Jiuzhou, Chen Guohong, Li Bichun
Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Yangzhou University, Yangzhou 225009, China.
Animals (Basel). 2021 Feb 6;11(2):425. doi: 10.3390/ani11020425.
Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) in vitro. Previously, a lentivirus induction strategy of introducing Oct4, Sox2, Nanog and Lin28 (OSNL) into the iPSC process has been shown as a possible way to produce chicken iPSCs from chicken embryonic fibroblasts, but the induction efficiency of this method was found to be significantly limiting. In order to help resolve this efficiency obstacle, this study seeks to clarify the associated regulation mechanisms and optimizes the reprogramming strategy of chicken iPSCs. This study showed that glycolysis and the expression of glycolysis-related genes correlate with a more efficient reprogramming process. At the same time, the transcription factors Oct4, Sox2 and Nanog were found to activate the expression of glycolysis-related genes. In addition, we introduced two small-molecule inhibitors (2i-SP) as a "glycolysis activator" together with the OSNL cocktail, and found that this significantly improved the induction efficiency of the iPSC process. As such, the study identifies direct molecular connections between core pluripotency factors and glycolysis during the chicken iPSC induction process and, with its results, provides a theoretical basis and technical support for chicken somatic reprogramming.
体细胞可在体外重编程为诱导多能干细胞（iPSC）。此前，一种将Oct4、Sox2、Nanog和Lin28（OSNL）导入iPSC过程的慢病毒诱导策略已被证明是从鸡胚胎成纤维细胞产生鸡iPSC的一种可能方法，但发现该方法的诱导效率存在显著局限性。为了帮助解决这一效率障碍，本研究旨在阐明相关调控机制并优化鸡iPSC的重编程策略。本研究表明，糖酵解及糖酵解相关基因的表达与更高效的重编程过程相关。同时，发现转录因子Oct4、Sox2和Nanog可激活糖酵解相关基因的表达。此外，我们将两种小分子抑制剂（2i-SP）作为“糖酵解激活剂”与OSNL混合物一起导入，发现这显著提高了iPSC过程的诱导效率。因此，该研究确定了鸡iPSC诱导过程中核心多能性因子与糖酵解之间的直接分子联系，并为鸡体细胞重编程提供了理论依据和技术支持。
