Homing of Mouse Spermatogonial Stem Cells to Germline Niche Depends on β1-integrin
Homing of Mouse Spermatogonial Stem Cells to Germline Niche Depends on β1-integrin
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DOI：
10.1016/j.stem.2008.08.002
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发表时间：
2008-11-06
期刊：
影响因子：
23.9
通讯作者：
Shinohara, Takashi
中科院分区：
文献类型：
--
作者：
Kanatsu-Shinohara, Mito;Takehashi, Masanori;Shinohara, Takashi
精原干细胞（SSCs）是精子发生的基础。以与造血干细胞移植类似的方式，ssc在输精管中注入微量后，定植在受体睾丸的生态位并重新启动精子发生。然而，对ssc的归巢机制知之甚少。在这里，我们研究了粘附分子在SSC归巢中的作用。从携带loxp标记的β 1-整合素等位基因的小鼠分离的ssc通过体外腺病毒cre转导进行消融，以表达β 1-整合素。β 1整合素突变体SSCs在体内重新定植受体睾丸的能力和在体外附着于层粘连蛋白分子的能力显著降低。相比之下，e -钙粘蛋白的基因消融并不影响归巢，e -钙粘蛋白突变的ssc完成了正常的精子发生。此外，支持细胞上β 1-整合素的缺失减少了SSC的归巢。这些结果表明- 1-整合素是SSC归巢的重要粘附受体，其与层粘连蛋白的关联在SSC归巢的多个步骤中至关重要。
Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis. In a manner comparable to hematopoietic stem cell transplantation, SSCs colonize the niche of recipient testes and reinitiate spermatogenesis following microinjection into the seminiferous tubules. However, little is known about the homing mechanism of SSCs. Here we examine the role of adhesion molecules in SSC homing. SSCs isolated from mice carrying loxP-tagged beta 1-integrin alleles were ablated for beta 1-integrin expression by in vitro adenoviral cre transduction. The beta 1-integrin mutant SSCs showed significantly reduced ability to recolonize recipient testes in vivo and to attach to laminin molecules in vitro. In contrast, genetic ablation of E-cadherin did not impair homing, and E-cadherin mutant SSCs completed normal spermatogenesis. In addition, the deletion of beta 1-integrin on Sertoli cells reduced SSC homing. These results identify beta 1-integrin as an essential adhesion receptor for SSC homing and its association with laminin is critical in multiple steps of SSC homing.