Chemokine (C-X-C) Ligand 12 Facilitates Trafficking of Donor Spermatogonial Stem Cells.
Chemokine (C-X-C) Ligand 12 Facilitates Trafficking of Donor Spermatogonial Stem Cells.
复制标题
DOI：
10.1155/2016/5796305
复制
发表时间：
2016
影响因子：
4.3
通讯作者：
Brinster RL
中科院分区：
文献类型：
--
作者：
Niu Z;Goodyear SM;Avarbock MR;Brinster RL
趋化因子（C-X-C）受体4型（CXCR 4）是原始生殖细胞（PGCs）的早期标志物，对PGCs的迁移和生殖腺的定殖至关重要。在精原干细胞（SSC）中，CXCR 4的表达由自我更新因子胶质细胞源性神经营养因子（GDNF）促进。在这里，我们证明了CXCR 4在供体小鼠精原干细胞重新占据受体睾丸内源性生态位过程中的重要作用。小鼠精原干细胞中CXCR 4表达的沉默显著减少了供体干细胞衍生集落的数量，而集落形态和精子发生与对照组相当。在归巢的关键窗口期间使用小分子抑制剂（AMD 3100）抑制CXCR 4信号传导也显著降低了供体来源的SSC在受体小鼠中建立生精集落的效率;然而，SSC的自我更新不受AMD 3100暴露的影响。相反，体外迁移测定证明了CXCR 4-CXCL 12信号传导在促进生殖细胞迁移中的影响。总之，这些研究表明，CXCR 4-CXCL 12信号传导功能促进SSC向干细胞龛归巢，并在重建精子发生中发挥关键作用。
The chemokine (C-X-C) receptor type 4 (CXCR4) is an early marker of primordial germ cells (PGCs) essential for their migration and colonization of the gonads. In spermatogonial stem cells (SSCs), the expression of CXCR4 is promoted by the self-renewal factor, glial cell line-derived neurotrophic factor (GDNF). Here, we demonstrate an important role of CXCR4 during donor mouse SSCs reoccupation of the endogenous niche in recipient testis. Silencing of CXCR4 expression in mouse SSCs dramatically reduced the number of donor stem cell-derived colonies, whereas colony morphology and spermatogenesis were comparable to controls. Inhibition of CXCR4 signaling using a small molecule inhibitor (AMD3100) during the critical window of homing also significantly lowered the efficiency of donor-derived SSCs to establish spermatogenic colonies in recipient mice; however, the self-renewal of SSCs was not affected by exposure to AMD3100. Rather, in vitro migration assays demonstrate the influence of CXCR4-CXCL12 signaling in promoting germ cell migration. Together, these studies suggest that CXCR4-CXCL12 signaling functions to promote homing of SSCs towards the stem cell niche and plays a critical role in reestablishing spermatogenesis.