Tu Jiongjiong, Fan Liqing, Tao Ke, Zhu Wenbing, Li Jianjun, Lu Guangxiu
National Center of Human Stem Cell Research and Engineering, Central South University, Changsha, Hunan 410078, China.
Reproduction. 2007 Dec;134(6):757-65. doi: 10.1530/REP-07-0161.
The stem cell factor (SCF), binding its tyrosine kinase receptor c-Kit, has been shown to play essential roles in the proliferation, differentiation, and survival of germline cells. However, few reports are available about the effect of SCF on the development of human gonocytes within the fetal testis. The objective of this study was to investigate whether SCF affects the biological behaviors of human gonocytes before or after they enter the mitotic arrest stage. Employing an organ culture system, we observed that addition of exogenous SCF could influence the morphology of human gonocytes in vitro. Moreover, SCF was able to trigger the colony formation of round gonocytes, which were characterized positive for alkaline phosphatase activity, Oct-4, SSEA-4, and c-Kit as well. We found that SCF exerted actions in a dose- and age-dependent manner, although the stimulatory effect lasted no more than 14 days. We also showed that SCF played a role in suppressing the apoptosis of human gonocytes. Blocking of SCF signaling with either phosphatidylinositol 3-kinase or mitogen-activated protein kinase inhibitor resulted in similar apoptotic features as well as the SCF-withdrawal cultures. Taken together, we report that SCF acts as a potent regulator in the fate determination of human gonocytes. Our studies should form the basis for in vitro studies and facilitate investigation of the molecular mechanisms underlying this unique stage.
干细胞因子（SCF）与其酪氨酸激酶受体c-Kit结合，已被证明在生殖细胞的增殖、分化和存活中发挥重要作用。然而，关于SCF对胎儿睾丸内人类生殖母细胞发育的影响，相关报道较少。本研究的目的是探讨SCF在人类生殖母细胞进入有丝分裂停滞阶段之前或之后是否会影响其生物学行为。利用器官培养系统，我们观察到添加外源性SCF可在体外影响人类生殖母细胞的形态。此外，SCF能够触发圆形生殖母细胞的集落形成，这些细胞碱性磷酸酶活性、Oct-4、SSEA-4和c-Kit均呈阳性。我们发现SCF以剂量和年龄依赖性方式发挥作用，尽管刺激作用持续不超过14天。我们还表明，SCF在抑制人类生殖母细胞凋亡方面发挥作用。用磷脂酰肌醇3激酶或丝裂原活化蛋白激酶抑制剂阻断SCF信号传导，会导致与SCF撤除培养物相似的凋亡特征。综上所述，我们报道SCF在人类生殖母细胞命运决定中起重要调节作用。我们的研究应为体外研究奠定基础，并有助于探究这一独特阶段的分子机制。
