College of Life Sciences, Inner Mongolia University, Xilingol South Road No. 49, Hohhot 010020, People's Republic of China.
Open Biol. 2023 Jan;13(1):220211. doi: 10.1098/rsob.220211. Epub 2023 Jan 25.
Ovarian organoids, based on female germline stem cells (FGSCs), are nowadays widely applied for reproductive medicine screening and exploring the potential mechanisms during mammalian oogenesis. However, there are still key issues that urgently need to be resolved in ovarian organoid technology, one of which is to establish a culture system that effectively expands FGSCs , as well as maintaining the unipotentcy of FGSCs to differentiate into oocytes. Here, FGSCs were EED226 treated and processed for examination of proliferation and differentiation . According to the results, EED226 specifically increased FGSC survival by decreasing the enrichment of H3K27me3 on promoter and exon, as well as enhancing OCT4 expression and inhibiting P53 and P63 expression. Notably, we also found that FGSCs with EED226 treatment differentiated into more oocytes during oogenesis , and the resultant oocytes maintained a low level of P63 versus control at early stage development. These results demonstrated that inhibition of EED activity appeared to promote the survival of FGSCs and markedly inhibited their apoptosis during differentiation. As a result of our study, we propose an effective culture strategy to culture FGSCs and obtain oocytes , which provides a new vision for oogenesis .
基于雌性生殖干细胞 (FGSCs) 的卵巢类器官，目前已广泛应用于生殖医学筛选，并探索哺乳动物卵发生过程中的潜在机制。然而，卵巢类器官技术仍存在一些亟待解决的关键问题，其中之一是建立一种能够有效扩增 FGSCs ，同时保持 FGSCs 向卵母细胞分化的单能性的培养体系。本研究中，通过 EED226 处理和检测，分析 FGSCs 的增殖和分化情况。结果表明，EED226 通过减少启动子和外显子上 H3K27me3 的富集，增强 OCT4 的表达，抑制 P53 和 P63 的表达，从而特异性地增加 FGSC 的存活。值得注意的是，我们还发现，经过 EED226 处理的 FGSCs 在卵发生过程中分化为更多的卵母细胞，并且与对照组相比，这些卵母细胞在早期发育阶段的 P63 水平较低。这些结果表明，抑制 EED 活性似乎促进了 FGSCs 的存活，并在分化过程中显著抑制了其凋亡。我们的研究提出了一种有效的 FGSCs 培养和获得卵母细胞的方法，为卵发生提供了新的视角。
