Differential expression of SOX17 and SOX2 in germ cells and stem cells has biological and clinical implications
Differential expression of SOX17 and SOX2 in germ cells and stem cells has biological and clinical implications
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DOI：
10.1002/path.2332
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发表时间：
2008-05-01
影响因子：
7.3
通讯作者：
Looijenga, L. H. J.
中科院分区：
文献类型：
--
作者：
de Jong, J.;Stoop, H.;Looijenga, L. H. J.
SOX和POU家族转录因子的联合作用在胚胎发育中起着重要作用。在胚胎干细胞中，SOX2和Pou5f1(Oct3/4)的结合对于维持未分化状态是必不可少的，因为它激活了与多潜能相关的基因，并抑制了参与分化的基因。除了胚胎干细胞，Pou5f1还存在于早期生殖细胞、原始生殖细胞和性腺细胞中，在这些细胞中，Pou5f1具有抑制凋亡的作用。在这里，我们证明SOX2在人胎儿性腺的生殖细胞中不存在，正如预期的那样，原位癌(CIS)，即青少年和成人睾丸生殖细胞肿瘤(TGCT)和精原细胞瘤的前驱病变。根据全基因组表达谱，发现SOX17而不是SOX2存在于早期生殖细胞及其恶性对应的CIS和精原细胞瘤中。免疫组织化学、Western印迹分析和定量RT-PCR分析表明，SOX17是区分精原细胞瘤和胚胎性癌的合适标记物，并在有代表性的细胞系中得到证实。支持细胞中可能存在SOX2的异常表达，当与CIS相关时，可能被误诊为胚胎性癌。总之，这项研究证明了SOX2在人类胚胎和恶性生殖细胞中不存在，这些细胞同时表达SOX17和Pou5f1。这一发现既具有诊断意义，也具有发育生物学意义。这可能是Pou5f1在正常生殖细胞和恶性生殖细胞中与胚胎干细胞功能不同的原因。版权所有(C)2008年大不列颠和爱尔兰病理学会。作者：John Wiley&Sons，Ltd.
Combined action of SOX and POU families of transcription factors plays major roles in embryonic development. In embryonic stem cells, the combination of SOX2 and POU5F1 (OCT3/4) is essential for maintaining the undifferentiated state by activating pluripotency-linked genes, and inhibition of genes involved in differentiation. Besides embryonic stem cells, POU5F1 is also present in early germ cells, primordial germ cells, and gonocytes, where it has a role in suppression of apoptosis. Here we demonstrate that SOX2 is absent in germ cells of human fetal gonads, and as expected carcinoma in situ (CIS), ie the precursor lesion of testicular germ cell tumours of adolescents and adults (TGCTs), and seminoma. Based on genome-wide expression profiling, SOX17 was found to be present, instead of SOX2, in early germ cells and their malignant counterparts, CIS and seminoma. Immunohistochemistry, western blot analysis, and quantitative RT-PCR showed that SOX17 is a suitable marker to distinguish seminoma from embryonal carcinoma, confirmed in representative cell lines. Aberrant SOX2 expression can be present in Sertoli cells when associated with CIS, which can be misdiagnosed as embryonal carcinoma. In conclusion, this study demonstrates the absence of SOX2 in human embryonic and malignant germ cells, which express SOX17 in conjunction with POU5F1. This finding has both diagnostic and developmental biological implications. It allows the identification of seminoma-like cells from embryonal carcinoma based on a positive marker and might be the explanation for the different function of POU5F1 in normal and malignant germ cells versus embryonic stem cells. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.