Volume 28, No 9, Sep 2018

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 28 Issue 9, September 2018: 879-896   |  Open Access

ORIGINAL ARTICLES

Single-cell RNA-seq uncovers dynamic processes and critical regulators in mouse spermatogenesis

Yao Chen 1, Yuxuan Zheng 2,3,4, Yun Gao 2,3,4, Zhen Lin 1, Suming Yang1, Tongtong Wang 1, Qiu Wang 1, Nannan Xie 1, Rong Hua 5,Mingxi Liu 5, Jiahao Sha 5, Michael D. Griswold 6, Jinsong Li 1, Fuchou Tang 2,3,4 and Ming-Han Tong 1

¹ State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; ² Beijing Advanced Innovation Center for Genomics, Biomedical Institute for Pioneering Investigation via Convergence, College of Life Sciences, Peking University, Beijing 100871, China; ³ Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China; ⁴ Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China; ⁵ State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China and ⁶ School of Molecular Biosciences and the Center for Reproductive Biology,Washington State University, Pullman, WA, USA Correspondence: Jinsong Li (jsli@sibcb.ac.cn) or Fuchou Tang (tangfuchou@pku.edu.cn) or Ming-Han Tong (minghan@sibcb.ac.cn)These authors contributed equally: Yao Chen, Yuxuan Zheng, Yun Gao, Zhen Lin, Suming Yang.

A systematic interrogation of male germ cells is key to complete understanding of molecular mechanisms governing spermatogenesis and the development of new strategies for infertility therapies and male contraception. Here we develop an approach to purify all types of homogeneous spermatogenic cells by combining transgenic labeling and synchronization of the cycle of the seminiferous epithelium, and subsequent single-cell RNA-sequencing. We reveal extensive and previously uncharacterized dynamic processes and molecular signatures in gene expression, as well as specific patterns of alternative splicing, and novel regulators for specific stages of male germ cell development. Our transcriptomics analyses led us to discover discriminative markers for isolating round spermatids at specific stages, and different embryo developmental potentials between early and late stage spermatids, providing evidence that maturation of round spermatids impacts on embryo development. This work provides valuable insights into mammalian spermatogenesis, and a comprehensive resource for future studies towards the complete elucidation of gametogenesis.

https://doi.org/10.1038/s41422-018-0074-y

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