What has single-cell RNA-seq taught us about mammalian spermatogenesis?

What has single-cell RNA-seq taught us about mammalian spermatogenesis?
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DOI:
10.1093/biolre/ioz088
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发表时间:
2019-05
影响因子:
3.6
通讯作者:
Shinnosuke Suzuki;Victoria D. Diaz;B. Hermann
Shinnosuke Suzuki;Victoria D. Diaz;B. Hermann
中科院分区:
生物学2区
文献类型:
--
作者:
Shinnosuke Suzuki;Victoria D. Diaz;B. Hermann

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哺乳动物精子发生是一个复杂的发育过程,它将有丝分裂的睾丸生殖细胞(精原细胞)转化为成熟的雄性配子(精子)以产生后代。几十年来,人们已经知道这个长达数周的过程涉及一系列高度有序和形态可识别的细胞变化,如精原细胞增殖,精母细胞进行减数分裂,精母细胞发育浓缩核,顶体和鞭毛。然而,驱动这些过程的许多潜在分子逻辑仍然不透明,因为传统的表征策略经常聚集细胞群以满足技术要求或由于细胞选择能力有限。最近,一个丰饶的单细胞转录组研究已经开始揭开基因表达、表型和生精发育背后的变化的完整纲要。这些数据集揭示了不同生精细胞类型之间先前模糊的分子异质性,并重新激活了睾丸生物学的研究。这篇综述描述了现有的生精细胞和睾丸体细胞单细胞RNA-seq图谱的范围,这些数据是如何产生和评估的,它们在推进精子发生知识方面的当前价值,以及它们在台式和床边的潜在未来用途。本文详细介绍了小鼠和人类生精细胞的一系列新的和革命性的单细胞RNA-seq结果,这些结果已经为睾丸功能的基本生物学概念提供了信息,对男性不育和避孕具有很高的翻译意义。
Abstract Mammalian spermatogenesis is a complex developmental program that transforms mitotic testicular germ cells (spermatogonia) into mature male gametes (sperm) for production of offspring. For decades, it has been known that this several-weeks-long process involves a series of highly ordered and morphologically recognizable cellular changes as spermatogonia proliferate, spermatocytes undertake meiosis, and spermatids develop condensed nuclei, acrosomes, and flagella. Yet, much of the underlying molecular logic driving these processes has remained opaque because conventional characterization strategies often aggregated groups of cells to meet technical requirements or due to limited capability for cell selection. Recently, a cornucopia of single-cell transcriptome studies has begun to lift the veil on the full compendium of gene expression phenotypes and changes underlying spermatogenic development. These datasets have revealed the previously obscured molecular heterogeneity among and between varied spermatogenic cell types and are reinvigorating investigation of testicular biology. This review describes the extent of available single-cell RNA-seq profiles of spermatogenic and testicular somatic cells, how those data were produced and evaluated, their present value for advancing knowledge of spermatogenesis, and their potential future utility at both the benchtop and bedside. Summary Sentence This review details the host of new and revolutionary single-cell RNA-seq results from mouse and human spermatogenic cells that are already informing basic biological concepts of testicular function with high translational significance for male infertility and contraception.