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人类精原干细胞:精母细胞性精原细胞瘤的一个可能起源。

Human spermatogonial stem cells: a possible origin for spermatocytic seminoma.

作者信息

Waheeb R, Hofmann M-C

机构信息

Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.

出版信息

Int J Androl. 2011 Aug;34(4 Pt 2):e296-305; discussion e305. doi: 10.1111/j.1365-2605.2011.01199.x.

DOI:10.1111/j.1365-2605.2011.01199.x
PMID:21790653
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3146023/
Abstract

In mammals, spermatogenesis is maintained throughout life by a small subpopulation of type A spermatogonia called spermatogonial stem cells (SSCs). In rodents, SSCs, or Asingle spermatogonia, form the self-renewing population. SSCs can also divide into Apaired (Apr) spermatogonia that are predestined to differentiate. Apaired spermatogonia produce chains of Aaligned (Aal) spermatogonia that divide to form A1 to A4, then type B spermatogonia. Type B spermatogonia will divide into primary spermatocytes that undergo meiosis. In human, there are only two different types of A spermatogonia, the Adark and Apale spermatogonia. The Adark spermatogonia are considered reserve stem cells, whereas the Apale spermatogonia are the self-renewing stem cells. There is only one generation of type B spermatogonia before differentiation into spermatocytes, which makes human spermatogenesis less efficient than in rodents. Although the biology of human SSCs is not well known, a panel of phenotypic markers has recently emerged that is remarkably similar to the list of markers expressed in mice. One such marker, the orphan receptor GPR125, is a plasma membrane protein that can be used to isolate human SSCs. Human SSCs proliferate in culture in response to growth factors such as GDNF, which is essential for SSC self-renewal in mice and triggers the same signalling pathways in both species. Therefore, despite differences in the spermatogonial differentiation scheme, both species use the same genes and proteins to maintain the pool of self-renewing SSCs within their niche. Spermatocytic seminomas are mainly found in the testes of older men, and they rarely metastasize. It is believed that these tumours originate from a post-natal germ cell. Because these lesions can express markers specific for meiotic prophase, they might originate from a primary spermatocyte. However, morphological appearance and overall immunohistochemical profile of these tumours indicate that the cell of origin could also be a spermatogonial stem cell.

摘要

在哺乳动物中,精子发生过程由一小部分被称为精原干细胞(SSCs)的A型精原细胞终生维持。在啮齿动物中,精原干细胞或单个A型精原细胞构成自我更新群体。精原干细胞也可分裂为注定要分化的配对A型(Apr)精原细胞。配对A型精原细胞产生成排的连接A型(Aal)精原细胞链,后者再分裂形成A1至A4型精原细胞,然后是B型精原细胞。B型精原细胞会分裂为进行减数分裂的初级精母细胞。在人类中,只有两种不同类型的A型精原细胞,即暗A型和亮A型精原细胞。暗A型精原细胞被认为是储备干细胞,而亮A型精原细胞是自我更新干细胞。在分化为精母细胞之前,只有一代B型精原细胞,这使得人类的精子发生效率低于啮齿动物。尽管人类精原干细胞的生物学特性尚不为人所知,但最近出现了一组表型标志物,与小鼠中表达的标志物清单惊人地相似。其中一个这样的标志物,孤儿受体GPR125,是一种可用于分离人类精原干细胞的质膜蛋白。人类精原干细胞在培养中会对生长因子如胶质细胞源性神经营养因子(GDNF)作出反应而增殖,GDNF对小鼠精原干细胞的自我更新至关重要,并且在两个物种中触发相同的信号通路。因此,尽管精原细胞分化模式存在差异,但两个物种都使用相同的基因和蛋白质来维持其微环境内自我更新的精原干细胞库。精母细胞性精原细胞瘤主要见于老年男性的睾丸,很少发生转移。据信这些肿瘤起源于出生后的生殖细胞。由于这些病变可表达减数分裂前期特异性标志物,它们可能起源于初级精母细胞。然而,这些肿瘤的形态外观和整体免疫组化特征表明,起源细胞也可能是精原干细胞。

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