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

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

doi:10.1186/s13578-021-00697-z

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

Cell Biosci. 2022 Jan 4;12(1):5. doi: 10.1186/s13578-021-00697-z.

Authors

Xiaopeng Hu^#¹, Hu Wang^#¹, Geng G Tian^#¹, Changliang Hou^#¹, Bo Xu¹, Xinyan Zhao², Yongqiang Zhao¹, Qian Fang¹, Xinyue Li¹, Lin He¹, Xuejin Chen³, Shangang Li^{4

5}, Ji Wu^{6

7

8}

Affiliations

¹ Bio-X Institutes, Shanghai Jiao Tong University, No. 800. Dongchuan Road, Minhang District, Shanghai, 200240, China.
² Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China.
³ Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
⁴ State Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China. Lisg@lpbr.cn.
⁵ Yunnan Key Laboratory of Primate Biomedicine Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650500, China. Lisg@lpbr.cn.
⁶ Bio-X Institutes, Shanghai Jiao Tong University, No. 800. Dongchuan Road, Minhang District, Shanghai, 200240, China. jiwu@sjtu.edu.cn.
⁷ Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China. jiwu@sjtu.edu.cn.
⁸ Shanghai Key Laboratory of Reproductive Medicine, Shanghai, 200025, China. jiwu@sjtu.edu.cn.

^# Contributed equally.

Abstract

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).

Results: We found that spermatogenesis was restarted by transplanting FGSCs into Kit^w/wv mutant testes. Complete meiosis and formation of SLCs was induced in vitro by testicular cells of Kit^w/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.

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.

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

Abstract

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