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

被引:270
作者
Chen, Yao [1 ]
Zheng, Yuxuan [2 ,3 ,4 ]
Gao, Yun [2 ,3 ,4 ]
Lin, Zhen [1 ]
Yang, Suming [1 ]
Wang, Tongtong [1 ]
Wang, Qiu [1 ]
Xie, Nannan [1 ]
Hua, Rong [5 ]
Liu, Mingxi [5 ]
Sha, Jiahao [5 ]
Griswold, Michael D. [6 ,7 ]
Li, Jinsong [1 ]
Tang, Fuchou [2 ,3 ,4 ]
Tong, Ming-Han [1 ]
机构
[1] Univ Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol,Shanghai Key Lab Mol Andro, Shanghai Inst Biochem & Cell Biol,Chinese Acad Sc, Shanghai 200031, Peoples R China
[2] Peking Univ, Coll Life Sci, Biomed Inst Pioneering Invest Via Convergence, Beijing Adv Innovat Ctr Genom, Beijing 100871, Peoples R China
[3] Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China
[4] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
[5] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 211166, Jiangsu, Peoples R China
[6] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA
[7] Washington State Univ, Ctr Reprod Biol, Pullman, WA 99164 USA
基金
中国国家自然科学基金;
关键词
GENE-EXPRESSION; MEIOTIC RECOMBINATION; CHROMOSOME SYNAPSIS; MALE MEIOSIS; GERM-CELLS; TRANSCRIPTOME; DIFFERENTIATION; VISUALIZATION; SPERMATIDS; PROTEIN;
D O I
10.1038/s41422-018-0074-y
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:879 / 896
页数:18
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