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利用多慢病毒转导和OAC2从体细胞生成鸡诱导多能干细胞(iPSCs)

Generation of chicken induced pluripotent stem cells (iPSCs) from somatic cells using multi-lentiviral transduction and OAC2.

作者信息

Liu Guangzheng, Zhu Xilin, Li Zeyu, Zhu Liqian, Chen Guohong, Niu Yingjie, Sun Hongyan, Zuo Qisheng, Song Jiuzhou, Han Wei, Wei Wanhong, Li Bichun, Jin Kai

机构信息

Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Yangzhou University, Yangzhou, 225009, China; 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; Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China; Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou, 225009, China.

出版信息

Theriogenology. 2025 Nov;247:117567. doi: 10.1016/j.theriogenology.2025.117567. Epub 2025 Jul 7.

DOI:
10.1016/j.theriogenology.2025.117567
PMID:40639260
Abstract

The chicken iPSCs have been successfully established and exhibit significant potential for the recovery and conservation of endangered avian species. However, the efficiency of induction remains quite limited. To enhance the induction system, a six-factor reprogramming approach incorporating OCT4, SOX2, NANOG, LIN28, KLF4, and C-MYC (OSNLKM) was employed via lentiviral infection, in combination with the small-molecule compound OAC2 and mouse embryonic fibroblast (MEF) feeder layers. The results demonstrated that the six-factor system significantly accelerated the reprogramming process and improved induction efficiency compared to the conventional four-factor system (OCT4, SOX2, NANOG, and LIN28; OSNL). Additionally, the MEF feeder layers were found to be essential for the successful reprogramming of chicken somatic cells. The inclusion of Oct4-activating compound 2 (OAC2) further optimized the reprogramming conditions, enabling the successful induction of iPSCs from chicken embryonic fibroblasts (CEFs) and Sertoli cells. Collectively, this study establishes an optimized reprogramming system for chicken somatic cells, enhancing iPSCs induction efficiency and expanding the potential applications of iPSCs technology in avian conservation and genetic modification.

摘要

鸡诱导多能干细胞(iPSCs)已成功建立,并在濒危鸟类物种的恢复和保护方面展现出巨大潜力。然而,诱导效率仍然相当有限。为了改进诱导系统,通过慢病毒感染采用了一种包含OCT4、SOX2、NANOG、LIN28、KLF4和C-MYC(OSNLKM)的六因子重编程方法,并结合小分子化合物OAC2和小鼠胚胎成纤维细胞(MEF)饲养层。结果表明,与传统的四因子系统(OCT4、SOX2、NANOG和LIN28;OSNL)相比,六因子系统显著加速了重编程过程并提高了诱导效率。此外,发现MEF饲养层对于鸡体细胞的成功重编程至关重要。Oct4激活化合物2(OAC2)的加入进一步优化了重编程条件,使得能够从鸡胚胎成纤维细胞(CEF)和支持细胞成功诱导出iPSCs。总体而言,本研究建立了一种针对鸡体细胞的优化重编程系统,提高了iPSCs的诱导效率,并扩展了iPSCs技术在鸟类保护和基因修饰方面的潜在应用。

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