The niche-derived glial cell line-derived neurotrophic factor (GDNF) induces migration of mouse spermatogonial stem/progenitor cells.

The niche-derived glial cell line-derived neurotrophic factor (GDNF) induces migration of mouse spermatogonial stem/progenitor cells.
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DOI:
10.1371/journal.pone.0059431
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Vicini E
Vicini E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Dovere L;Fera S;Grasso M;Lamberti D;Gargioli C;Muciaccia B;Lustri AM;Stefanini M;Vicini E

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在哺乳动物中,干细胞/祖细胞室的生物活性通过精子发生维持成熟配子的产生。精原干细胞及其后代属于未分化精原细胞,是一种在精小管基膜上发现的生殖细胞群。大量证据表明,神经胶质细胞系衍生的神经营养因子(GDNF)是体内和体外干细胞自我更新所必需的。然而,这种活动背后的机制尚不完全清楚。在这项研究中,我们发现GDNF诱导新选择的未分化精原细胞以及培养的种系干细胞的剂量依赖性定向迁移,使用Boyden室试验。GDNF诱导的迁移依赖于GDNF共受体GFRA1的表达,对亲代和GFRA1转导的GC-1精原细胞系进行的迁移实验表明。我们发现肌动蛋白调节蛋白血管扩张剂刺激磷蛋白(VASP)在未分化精原细胞中特异性表达。VASP属于参与肌动蛋白依赖过程的ENA/VASP蛋白家族,如成纤维细胞迁移、轴突引导和细胞粘附。在完整的精管和种系干细胞培养中,GDNF处理以剂量依赖的方式上调VASP。这些数据确定了小生境衍生因子GDNF的新作用,并表明GDNF可能影响干细胞/祖细胞室,影响肌动蛋白细胞骨架和细胞迁移。
In mammals, the biological activity of the stem/progenitor compartment sustains production of mature gametes through spermatogenesis. Spermatogonial stem cells and their progeny belong to the class of undifferentiated spermatogonia, a germ cell population found on the basal membrane of the seminiferous tubules. A large body of evidence has demonstrated that glial cell line-derived neurotrophic factor (GDNF), a Sertoli-derived factor, is essential for in vivo and in vitro stem cell self-renewal. However, the mechanisms underlying this activity are not completely understood. In this study, we show that GDNF induces dose-dependent directional migration of freshly selected undifferentiated spermatogonia, as well as germline stem cells in culture, using a Boyden chamber assay. GDNF-induced migration is dependent on the expression of the GDNF co-receptor GFRA1, as shown by migration assays performed on parental and GFRA1-transduced GC-1 spermatogonial cell lines. We found that the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP) is specifically expressed in undifferentiated spermatogonia. VASP belongs to the ENA/VASP family of proteins implicated in actin-dependent processes, such as fibroblast migration, axon guidance, and cell adhesion. In intact seminiferous tubules and germline stem cell cultures, GDNF treatment up-regulates VASP in a dose-dependent fashion. These data identify a novel role for the niche-derived factor GDNF, and they suggest that GDNF may impinge on the stem/progenitor compartment, affecting the actin cytoskeleton and cell migration.
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