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; Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Yangzhou University, Yangzhou 225009, China.
Animal & Avian Sciences, University of Maryland, College Park, MA 20742, USA.
Poult Sci. 2024 Nov;103(11):104140. doi: 10.1016/j.psj.2024.104140. Epub 2024 Aug 8.
Avian primordial germ cells (PGCs) are important culture cells for the production of transgenic chickens and preservation of the genetic resources of endangered species; however, culturing these cells in vitro proves challenging. Although the proliferation of chicken PGCs is dependent on insulin, the underlying molecular mechanisms remain unclear. In the present study, we explored the expression of the PI3K/AKT signaling pathway in PGCs, investigated its effects on PGC self-renewal and biological properties, and identified the underlying mechanisms. Our findings indicated that although supplementation with the PI3K/AKT activator IGF-1 failed to promote proliferation under the assessed culture conditions, the PI3K/AKT inhibitor LY294002 resulted in retarded cell proliferation and reduced expression of germ cell-related markers. We further demonstrated that inhibition of PI3K/AKT regulates the cell cycle and promotes apoptosis in PGCs by activating the expression of BAX and inhibiting that of Bcl-2. These findings indicated that the PI3K/AKT pathway is required for cell renewal, apoptosis, and maintenance of the reproductive potential in chicken PGCs. This study aimed to provide a theoretical basis for the optimization and improvement of a culture system for chicken PGCs and provide insights into the self-renewal of vertebrate PGCs as well as potential evolutionary changes in this unique cell population.
禽类原始生殖细胞(PGCs)是生产转基因鸡和保存濒危物种遗传资源的重要培养细胞;然而,体外培养这些细胞具有挑战性。尽管鸡 PGC 的增殖依赖于胰岛素,但其中的分子机制尚不清楚。在本研究中,我们研究了 PI3K/AKT 信号通路在 PGC 中的表达,探讨了其对 PGC 自我更新和生物学特性的影响,并鉴定了潜在的机制。研究结果表明,尽管添加 PI3K/AKT 激活剂 IGF-1 未能在评估的培养条件下促进增殖,但 PI3K/AKT 抑制剂 LY294002 导致细胞增殖迟缓,生殖细胞相关标志物表达减少。我们进一步证明,PI3K/AKT 的抑制通过激活 BAX 的表达和抑制 Bcl-2 的表达来调节 PGC 中的细胞周期并促进细胞凋亡。这些发现表明,PI3K/AKT 途径对于鸡 PGC 的细胞更新、凋亡和生殖潜能的维持是必需的。本研究旨在为鸡 PGC 培养系统的优化和改进提供理论基础,并深入了解脊椎动物 PGC 的自我更新以及该独特细胞群体的潜在进化变化。