The adult human testis transcriptional cell atlas.

The adult human testis transcriptional cell atlas.
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DOI:
10.1038/s41422-018-0099-2
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发表时间:
2018-12
期刊:
影响因子:
44.1
通讯作者:
Cairns BR
Cairns BR
中科院分区:
生物学1区
文献类型:
--
作者:
Guo J;Grow EJ;Mlcochova H;Maher GJ;Lindskog C;Nie X;Guo Y;Takei Y;Yun J;Cai L;Kim R;Carrell DT;Goriely A;Hotaling JM;Cairns BR

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人类成年精子发生平衡精原干细胞(SSC)的自我更新和分化,以及复杂的生殖细胞与生态位相互作用,以确保长期生育和忠实的基因组繁殖。在这里,我们对来自年轻人的6500个睾丸细胞进行了单细胞RNA测序。我们发现了5种生态位/体细胞类型(间质细胞、肌样细胞、支持细胞、内皮细胞、巨噬细胞),并观察了生殖系-生态位相互作用和关键的人-鼠差异。精子发生,包括减数分裂,通过计算重建,揭示了顺序编码、非编码和重复元件转录特征。有趣的是,我们确定了五种离散的转录/发育精原状态,其中包括一种新的早期SSC状态,称为状态0。表观遗传学特征和新生转录分析表明,精原状态具有发育可塑性。为了了解状态0的起源,我们分析了婴儿的睾丸细胞,并确定了成人状态0和婴儿SSCs之间的明显相似之处。总体而言,我们的数据集描述了正常成人睾丸的关键转录和表观遗传学特征,并为生殖细胞发育过渡和可塑性提供了新的见解。
Human adult spermatogenesis balances spermatogonial stem cell (SSC) self-renewal and differentiation, alongside complex germ cell-niche interactions, to ensure long-term fertility and faithful genome propagation. Here, we performed single-cell RNA sequencing of ~6500 testicular cells from young adults. We found five niche/somatic cell types (Leydig, myoid, Sertoli, endothelial, macrophage), and observed germline-niche interactions and key human-mouse differences. Spermatogenesis, including meiosis, was reconstructed computationally, revealing sequential coding, non-coding, and repeat-element transcriptional signatures. Interestingly, we identified five discrete transcriptional/developmental spermatogonial states, including a novel early SSC state, termed State 0. Epigenetic features and nascent transcription analyses suggested developmental plasticity within spermatogonial States. To understand the origin of State 0, we profiled testicular cells from infants, and identified distinct similarities between adult State 0 and infant SSCs. Overall, our datasets describe key transcriptional and epigenetic signatures of the normal adult human testis, and provide new insights into germ cell developmental transitions and plasticity.
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