Elucidating human male germ cell development by studying germ cell cancer.
Elucidating human male germ cell development by studying germ cell cancer.
复制标题
DOI：
10.1530/rep-16-0114
复制
发表时间：
2016-10
期刊：
影响因子：
3.8
通讯作者：
D. Nettersheim;S. Jostes;S. Schneider;H. Schorle
中科院分区：
文献类型：
--
作者：
D. Nettersheim;S. Jostes;S. Schneider;H. Schorle
人类生殖细胞的发育受到复杂的调控网络以时空方式的调控。在这里，我们总结了在生殖细胞肿瘤和各自细胞系中获得的结果，并试图找出与正常生殖细胞发育的相似之处。这种比较可以推测关键且容易出错的机制，当这些机制受到干扰时，会导致生殖细胞肿瘤的发展。规范化后不久，原始生殖细胞表达多能性标记，在人类中，这种标记一直持续到胎儿/婴儿精原细胞阶段。除了罕见的精母细胞肿瘤外，几乎所有精原细胞瘤和胚胎癌都表达多能性标记，并显示出多能性或全能性的迹象。因此，就肿瘤生物学而言，正确处理多能性程序似乎是生殖细胞发育中最关键的步骤。此外，来自小鼠的数据表明，生殖细胞显示出表观遗传特征，这与多能细胞高度相似。这种特征（稳定的组蛋白密码、DNA 低甲基化）是受精时快速诱导全能性和多能性所必需的。我们认为，成年精原细胞在暴露于内分泌干扰物或表观遗传活性物质时，很容易重新启动多能性程序，从而产生生殖细胞肿瘤。多能细胞可以源自成年小鼠和人类睾丸细胞的事实进一步证实了这一想法。
Human germ cell development is regulated in a spatio-temporal manner by complex regulatory networks. Here, we summarize results obtained in germ cell tumors and respective cell lines and try to pinpoint similarities to normal germ cell development. This comparison allows speculating about the critical and error-prone mechanisms, which when disturbed, lead to the development of germ cell tumors. Short after specification, primordial germ cells express markers of pluripotency, which, in humans, persists up to the stage of fetal/infantile spermatogonia. Aside from the rare spermatocytic tumors, virtually all seminomas and embryonal carcinomas express markers of pluripotency and show signs of pluripotency or totipotency. Therefore, it appears that proper handling of the pluripotency program appears to be the most critical step in germ cell development in terms of tumor biology. Furthermore, data from mice reveal that germline cells display an epigenetic signature, which is highly similar to pluripotent cells. This signature (poised histone code, DNA hypomethylation) is required for the rapid induction of toti- and pluripotency upon fertilization. We propose that adult spermatogonial cells, when exposed to endocrine disruptors or epigenetic active substances, are prone to reinitiate the pluripotency program, giving rise to a germ cell tumor. The fact that pluripotent cells can be derived from adult murine and human testicular cells further corroborates this idea.