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

Single-cell RNA-seq uncovers dynamic processes and critical regulators in mouse spermatogenesis.
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单细胞 RNA-seq 揭示小鼠精子发生的动态过程和关键调节因子

DOI:
10.1038/s41422-018-0074-y
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发表时间:
2018-09
期刊:
影响因子:
44.1
通讯作者:
Tong MH
Tong MH
中科院分区:
生物学1区
文献类型:
--
作者:
Chen Y;Zheng Y;Gao Y;Lin Z;Yang S;Wang T;Wang Q;Xie N;Hua R;Liu M;Sha J;Griswold MD;Li J;Tang F;Tong MH

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对男性生殖细胞的系统研究是完全理解精子发生的分子机制以及开发不育治疗和男性避孕新策略的关键。在这里,我们开发了一种方法来纯化所有类型的同质生精细胞,结合转基因标记和同步的生精上皮细胞周期,以及随后的单细胞RNA测序。我们揭示了广泛的和以前未表征的动态过程和基因表达的分子特征,以及选择性剪接的特定模式,和男性生殖细胞发育的特定阶段的新型调节剂。我们的转录组学分析使我们发现了在特定阶段分离圆形精子细胞的区别性标记,以及早期和晚期精子细胞之间不同的胚胎发育潜力,为圆形精子细胞的成熟影响胚胎发育提供了证据。这项工作为哺乳动物精子发生提供了有价值的见解,并为未来的研究提供了全面的资源,以完全阐明配子发生。
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.
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发表时间: 2015-01-15
期刊: Bioinformatics (Oxford, England)
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