Characterization of spermatogonial stem cells lacking intercellular bridges and genetic replacement of a mutation in spermatogonial stem cells.
Characterization of spermatogonial stem cells lacking intercellular bridges and genetic replacement of a mutation in spermatogonial stem cells.
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DOI：
10.1371/journal.pone.0038914
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Matzuk MM
中科院分区：
文献类型：
--
作者：
Iwamori N;Iwamori T;Matzuk MM
干细胞在再生医学中具有基因治疗的潜力。在各种干细胞中，精原干细胞有一个独特的特点，邻近的细胞可以通过细胞间桥连接起来。然而，细胞间桥在干细胞自我更新、分化和增殖中的作用仍有待阐明。在这里，我们不仅展示了缺乏细胞间桥的睾丸表达基因14 （TEX14）无精原干细胞的特征，而且还展示了在精原干细胞中对突变进行基因校正的试验应用，作为未来基因治疗的模型。在TEX14缺失的睾丸中，一些对未分化精原细胞重要的基因以及一些与分化相关的基因被激活。令人惊讶的是，TEX14空精原干细胞可以形成链状结构，即使它们不能形成稳定的细胞间桥。培养的TEX14阴性精原干细胞同时具有未分化精原细胞和已分化精原细胞的特征。由于CDK4抑制剂的上调和细胞周期蛋白e的下调，TEX14缺失的精原干细胞无法长期培养。这些结果表明，细胞间桥对于维持精原干细胞及其增殖都是必不可少的。最后，在体外用同源重组成功地取代了Tex14+/−精原干细胞的突变。本研究为精原干细胞的长期培养提供了生殖医学的治疗潜力。
Stem cells have a potential of gene therapy for regenerative medicine. Among various stem cells, spermatogonial stem cells have a unique characteristic in which neighboring cells can be connected by intercellular bridges. However, the roles of intercellular bridges for stem cell self-renewal, differentiation, and proliferation remain to be elucidated. Here, we show not only the characteristics of testis-expressed gene 14 (TEX14) null spermatogonial stem cells lacking intercellular bridges but also a trial application of genetic correction of a mutation in spermatogonial stem cells as a model for future gene therapy. In TEX14 null testes, some genes important for undifferentiated spermatogonia as well as some differentiation-related genes were activated. TEX14 null spermatogonial stem cells, surprisingly, could form chain-like structures even though they do not form stable intercellular bridges. TEX14 null spermatogonial stem cells in culture possessed both characteristics of undifferentiated and differentiated spermatogonia. Long-term culture of TEX14 null spermatogonial stem cells could not be established likely secondary to up-regulation of CDK4 inhibitors and down-regulation of cyclin E. These results suggest that intercellular bridges are essential for both maintenance of spermatogonial stem cells and their proliferation. Lastly, a mutation in Tex14+/− spermatogonial stem cells was successfully replaced by homologous recombination in vitro. Our study provides a therapeutic potential of spermatogonial stem cells for reproductive medicine if they can be cultured long-term.
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影响因子：
23.9
作者：
Ko, Kinarm;Tapia, Natalia;Schoeler, Hans R.
通讯作者：
Schoeler, Hans R.
影响因子：
3.6
作者：
Naughton, CK;Jain, S;Milbrandt, J
通讯作者：
Milbrandt, J
影响因子：
2.7
作者：
Greenbaum, Michael P.;Ma, Lang;Matzuk, Martin M.
通讯作者：
Matzuk, Martin M.
影响因子：
7.2
作者：
Greenbaum, Michael P.;Iwamori, Tokuko;Matzuk, Martin M.
通讯作者：
Matzuk, Martin M.
影响因子：
--
作者：
HUCKINS, C;OAKBERG, EF
通讯作者：
OAKBERG, EF