Offspring production of haploid spermatid-like cells derived from mouse female germline stem cells with chromatin condensation

来自具有染色质凝聚的小鼠雌性生殖系干细胞的单倍体精子细胞样细胞的后代产生

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作者:Xiaopeng Hu #, Hu Wang #, Geng G Tian #, Changliang Hou #, Bo Xu, Xinyan Zhao, Yongqiang Zhao, Qian Fang, Xinyue Li, Lin He, Xuejin Chen, Shangang Li, Ji Wu

Background

During male meiosis, the Y chromosome can form perfect pairing with the X chromosome. However, it is unclear whether mammalian Female germline stem cells (FGSCs) without a Y chromosome can transdifferentiate into functional haploid spermatid-like cells (SLCs).

Conclusion

This study demonstrates that sperm can be produced from FGSCs without a Y chromosome. This suggests a strategy for dairy cattle breeding to produce only female offspring with a high-quality genetic background.

Results

We found that spermatogenesis was restarted by transplanting FGSCs into Kitw/wv mutant testes. Complete meiosis and formation of SLCs was induced in vitro by testicular cells of Kitw/wv mutant mice, cytokines and retinoic acid. Healthy offspring were produced by sperm and SLCs derived from the in vivo and in vitro transdifferentiation of FGSCs, respectively. Furthermore, high-throughput chromosome conformation capture sequencing(Hi-C-seq) and "bivalent" (H3K4me3-H3K27me3) micro chromatin immunoprecipitation sequencing (μChIP-seq) experiments showed that stimulated by retinoic acid gene 8 (STRA8)/protamine 1 (PRM1)-positive transdifferentiated germ cells (tGCs) and male germ cells (mGCs) display similar chromatin dynamics and chromatin condensation during in vitro spermatogenesis.

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