Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis

Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis
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DOI:
10.1016/j.ydbio.2004.01.036
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发表时间:
2004-05-13
影响因子:
2.7
通讯作者:
Nabeshima, Y
Nabeshima, Y
中科院分区:
生物学3区
文献类型:
--
作者:
Yoshida, S;Takakura, A;Nabeshima, Y

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在哺乳动物睾丸中,典型的干细胞系统确保精子的连续产生。一系列的实验表明,干细胞活性存在于最原始的小的生殖细胞亚群中,即A(s)(A(单个))、A(pr)(A(配对))和A(al)(A(排列))精原细胞,也统称为未分化精原细胞。然而,它们的细胞或分子性质在很大程度上有待阐明,因为尚未鉴定出在这些细胞中特异性表达的基因,这使得研究它们变得困难。在这项研究中,我们证明了一个B类碱性螺旋-环-螺旋(bHLH)转录因子神经生成素3(ngn 3)的表达,特别是在作为,四月,和A,精原细胞,因为ngn 3表达在c-Kit阴性精原细胞在整个生精周期,和转基因标记与绿色荧光蛋白显示连接1,2,4,8,16,或32 ngn 3阳性细胞通过细胞间桥。ngn 3首先在c-Kit阴性的精子原细胞前的青春期前阶段表达。使用Cre-loxP系统的谱系追踪表明,ngn 3阳性生殖细胞最终导致成熟睾丸中所有的精子发生。据我们所知,ngn 3是第一个报道的基因,描绘这些精子发生的最早阶段。考虑到ngn 3的分子特性,它可能参与了它们的分化调控。此外,绿色荧光蛋白的可视化和外源基因的靶向表达是研究哺乳动物生精干细胞系统的有价值的工具。(C)2004年爱思唯尔公司All rights reserved.
in mammalian testis, a typical stem cell system ensures continuous spermatozoa production. Lines of experiments have demonstrated that stem cell activity resides in the most primitive small subset of germ cells, that is, A(s) (A(single)), A(pr) (A(paired)), and A(al) (A(aligned)) spermatogonia, also collectively called undifferentiated spermatogonia. However, their cellular or molecular nature is largely to be elucidated because a gene that is specifically expressed in these cells has not yet been identified, which makes it difficult to study them. In this study, we demonstrate that a class B basic helix-loop-helix (bHLH) transcription factor neurogenin3 (ngn3) is expressed specifically in As, Apr, and A,, spermatogonia because ngn3 is expressed in c-Kit negative spermatogonia throughout the seminiferous cycle, and transgenic labeling with GFP revealed connection of 1, 2, 4, 8, 16, or 32 ngn3-positive cells via intercellular bridges. ngn3 is first expressed at the prepubertal stage in c-Kit negative prespermatogonia. Lineage tracing, using the Cre-loxP system, demonstrates that ngn3-positive germ cells give rise to eventually all the spermatogenesis in mature testis. To our knowledge, ngn3 is the first reported gene that delineates these earliest stages of spermatogenesis. Considering its molecular nature, ngn3 could be involved in their differentiation control. Moreover, visualization with GFP and targeting expression of exogenous genes are valuable tools to investigate the mammalian spermatogenic stem cell system. (C) 2004 Elsevier Inc. All rights reserved.