Meiosis resumption in human primordial germ cells from induced pluripotent stem cells by in vitro activation and reconstruction of ovarian ... View Full Text


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Article Info

DATE

2022-07-26

AUTHORS

Sheng Yang, Zhen Liu, Shengda Wu, Lang Zou, Yanpei Cao, Hongjia Xu, Jingfeng Huang, Qingyan Tian, Fanggui Wu, Panpan Li, Shuping Peng, Cijun Shuai

ABSTRACT

BackgroundThe differentiation of human induced pluripotent stem cells (iPSCs) into oocytes, which involves the transformation from mitosis to meiosis, has been a hotspot of biological research for many years and represents a desirable experimental model and potential strategy for treating infertility. At present, studies have shown that most cells stagnate in the oogonium stage after differentiation into primordial germ cells (PGCs) from human iPSCs.MethodsiPSCs carrying a SYCP3-mkate2 knock-in reporter were generated by the CRISPR/Cas9 strategy to monitor meiosis status during induced differentiation from iPSCs into oocytes. These induced PGCs/oogonia were activated by small molecules from the Wnt signaling pathway and then cocultured with reconstructed human ovarian nests in vivo for further development.ResultsFirst, human PGCs and oogonia were efficiently induced from iPSCs. Second, induced dormant PGCs resumed meiosis and then differentiated into primary oocytes through the in vitro activation of the Wnt signaling pathway. Finally, a new coculture system involving the reconstruction of ovarian nests in vitro could facilitate the differentiation of oocytes.ConclusionsHuman PGCs/oogonia induced from iPSCs can be activated and used to resume meiosis by molecules of the Wnt signaling pathway. The coculture of activated PGCs and reconstruction of ovarian nests facilitated differentiation into primary oocytes and the generation of haploid human oocytes in vivo. These findings established a new strategy for germline competence in primary oocytes and provided a keystone for human gametogenesis in vitro and in vivo. More... »

PAGES

339

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13287-022-03019-3

DOI

http://dx.doi.org/10.1186/s13287-022-03019-3

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https://app.dimensions.ai/details/publication/pub.1149784433

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35883163


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