Niu Zhiyv, Goodyear Shaun M, Avarbock Mary R, Brinster Ralph L
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA.
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Stem Cells Int. 2016;2016:5796305. doi: 10.1155/2016/5796305. Epub 2016 Jan 21.
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.
趋化因子（C-X-C）受体4型（CXCR4）是原始生殖细胞（PGC）的早期标志物，对其向性腺迁移和定殖至关重要。在精原干细胞（SSC）中，CXCR4的表达受自我更新因子胶质细胞系源性神经营养因子（GDNF）的促进。在此，我们证明了CXCR4在供体小鼠SSC重新占据受体睾丸内源性微环境过程中的重要作用。小鼠SSC中CXCR4表达的沉默显著减少了供体干细胞衍生克隆的数量，而克隆形态和精子发生与对照组相当。在归巢的关键窗口期使用小分子抑制剂（AMD3100）抑制CXCR4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克隆的效率；然而，SSC的自我更新不受AMD3100暴露的影响。相反，体外迁移试验证明了CXCR4-CXCL12信号传导在促进生殖细胞迁移中的作用。总之，这些研究表明CXCR4-CXCL12信号传导的功能是促进SSC归巢到干细胞微环境，并在重建精子发生中起关键作用。
