Identification of Rat Testicular Leydig Precursor Cells by Single-Cell-RNA-Sequence Analysis.

Identification of Rat Testicular Leydig Precursor Cells by Single-Cell-RNA-Sequence Analysis.
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通过单细胞 RNA 序列分析鉴定大鼠睾丸间质前体细胞

DOI:
10.3389/fcell.2022.805249
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发表时间:
2022
影响因子:
5.5
通讯作者:
Chen H
Chen H
中科院分区:
生物学2区
文献类型:
--
作者:
Guan X;Chen P;Ji M;Wen X;Chen D;Zhao X;Huang F;Wang J;Shao J;Xie J;Zhao X;Chen F;Tian J;Lin H;Zirkin BR;Duan P;Su Z;Chen H

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干细胞(Stem Leydig cells, SLCs)在成年间质细胞(Leydig cell, ALC)群体的发育和维持中起着至关重要的作用。SLCs也存在于成人睾丸中。它们在成年睾丸中的鉴定、特征和调节仍不确定。使用单细胞RNA-seq,我们发现间充质间质群体可能参与ALC再生。在ALC消除后,一部分基质细胞开始增殖,而另一部分基质细胞开始分化为ALC。转录组学分析确定了5个基质簇,可分为两大类,分别代表增殖和分化群体。增殖组代表高水平表达CD90、Nes、Lum、Fn和Gap43的干细胞。分化组代表一个准备形成ALCs的祖细胞阶段,特异表达Vtn、Rasl11a、Id1和Egr2。观察到ALC丧失后活跃分裂的细胞并不是那些形成ALC的细胞,这表明干细胞的增殖和分化是分开调节的,基质干细胞库的维持发生在群体水平上。该研究还确定了主要间质细胞群的特异性标记物和参与SLCs调节的潜在旁分泌因子。我们的数据提出了一个关于SLC身份、增殖、分化和调控的新理论。
Stem Leydig cells (SLCs) play a critical role in the development and maintenance of the adult Leydig cell (ALC) population. SLCs also are present in the adult testis. Their identification, characteristics, and regulation in the adult testis remain uncertain. Using single-cell RNA-seq, we found that the mesenchymal stromal population may be involved in ALC regeneration. Upon ALC elimination, a fraction of stromal cells begins to proliferate while a different fraction begins to differentiate to ALCs. Transcriptomic analysis identified five stromal clusters that can be classified into two major groups representing proliferation and differentiation populations. The proliferating group represents stem cells expressing high levels of CD90, Nes, Lum, Fn and Gap43. The differentiating group represents a progenitor stage that is ready to form ALCs, and specifically expresses Vtn, Rasl11a, Id1 and Egr2. The observation that the actively dividing cells after ALC loss were not those that formed ALCs suggests that stem cell proliferation and differentiation are regulated separately, and that the maintenance of the stromal stem cell pool occurs at the population level. The study also identified specific markers for the major interstitial cell groups and potential paracrine factors involved in the regulation of SLCs. Our data suggest a new theory about SLC identity, proliferation, differentiation, and regulation.
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