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

Cell & Bioscience

Bo Xu¹  Geng. G. Tian¹  Xinyue Li¹  Hu Wang¹  Lin He¹  Yongqiang Zhao¹  Xiaopeng Hu¹  Qian Fang¹  Changliang Hou¹  Ji Wu²  Xuejin Chen³  Xinyan Zhao⁴  Shangang Li⁵ 

[1] Bio-X Institutes, Shanghai Jiao Tong University, No. 800. Dongchuan Road, Minhang District, 200240, Shanghai, China;Bio-X Institutes, Shanghai Jiao Tong University, No. 800. Dongchuan Road, Minhang District, 200240, Shanghai, China;Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China;Shanghai Key Laboratory of Reproductive Medicine, 200025, Shanghai, China;Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, 200025, Shanghai, China;Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China;State Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, 650500, Kunming, China;Yunnan Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, 650500, Kunming, China;

关键词: Female germline stem cells;    Transdifferentiation;    In vitro spermatogenesis;    Spermatid-like cells;    High-throughput chromosome conformation capture sequencing;    Bivalent;   

DOI  :  10.1186/s13578-021-00697-z

来源: Springer

【 摘 要 】

BackgroundDuring 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).ResultsWe 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.ConclusionThis 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.

【 授权许可】

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