Expression of pluripotent stem cell markers in the human fetal testis
Expression of pluripotent stem cell markers in the human fetal testis
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DOI：
10.1634/stemcells.2007-0605
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发表时间：
2008-02-01
期刊：
影响因子：
5.2
通讯作者：
Gearhart, John D.
中科院分区：
文献类型：
--
作者：
Kerr, Candace L.;Hill, Christine M.;Gearhart, John D.
人类原始生殖细胞（PGCs）已被证明是称为胚胎生殖细胞（EGCs）的多能干细胞的来源。然而，这些细胞在胎儿性腺中的发育潜能仍然是难以捉摸的。因此，本研究提供了一个多能和生殖细胞标志物表达的人胎儿睾丸受精后7 - 15周（pF）的综合分析，并比较这种表达的能力，以获得EGCs。虽然大多数生殖细胞表达干细胞标志物阶段特异性胚胎抗原（SSEA）1，SSEA 4，EMA-1和碱性磷酸酶，但只有一小部分（< 1%）表达OCT 4，CKIT和NANOG。具体而言，在第7 - 9周期间，发育中的脐带中OCT 4（+）/ CKIT+/NANOG（+）细胞的数量显著增加，随后逐渐下降至第15周pF。到第15周pF，在睾丸周围的脐带中发现剩余的OCT 4（+）/CKIT+/NANOG（+）细胞，并且主要的生殖细胞，CKIT+细胞，不再表达OCT 4或NANOG。基于形态学和早期生殖细胞标志物的表达，包括VASA，DAZL，我们认为这些细胞是有丝分裂活跃的生殖细胞或前精原细胞。重要的是，OCT 4（+）细胞的数量与培养物中衍生的EGC集落数量的增加相关。有趣的是，两个多能标记物，Tra-1 - 60和Tra-1 - 81，虽然在EGCs中高度表达，但在性腺中的PGCs中不表达。总之，这些结果表明，PGCs保持表达的多能干细胞标志物在性腺的性分化过程中和之后，虽然在非常低的数字。
Human primordial germ cells (PGCs) have proven to be a source of pluripotent stem cells called embryonic germ cells (EGCs). However, the developmental potency of these cells in the fetal gonad still remains elusive. Thus, this study provides a comprehensive analysis of pluripotent and germ cell marker expression in human fetal testis 7 - 15 weeks postfertilization (pF) and compares this expression to their ability to derive EGCs. Although the majority of germ cells expressed stem cell markers stage-specific embryonic antigen (SSEA) 1, SSEA4, EMA-1, and alkaline phosphatase, only a small percentage of those (< 1%) expressed OCT4, CKIT, and NANOG. Specifically, the number of OCT4(+)/ CKIT+/NANOG(+) cells significantly increased in the developing cords during weeks 7 - 9, followed by a gradual decline into week 15 pF. By week 15 pF, the remaining OCT4(+)/CKIT+/NANOG(+) cells were found in the cords surrounding the periphery of the testis, and the predominant germ cells, CKIT+ cells, no longer expressed OCT4 or NANOG. Based on morphology and early germ cell marker expression, including VASA, PUM2, and DAZL, we suggest these cells are mitotically active gonocytes or prespermatogonia. Importantly, the number of OCT4(+) cells correlated with an increase in the number of EGC colonies derived in culture. Interestingly, two pluripotent markers, Tra-1 - 60 and Tra-1 - 81, although highly expressed in EGCs, were not expressed by PGCs in the gonad. Together, these results suggest that PGCs maintain expression of pluripotent stem cell markers during and after sexual differentiation of the gonad, albeit in very low numbers.