ETV5 regulates sertoli cell chemokines involved in mouse stem/progenitor spermatogonia maintenance.
ETV5 regulates sertoli cell chemokines involved in mouse stem/progenitor spermatogonia maintenance.
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DOI：
10.1002/stem.508
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发表时间：
2010-10
期刊：
影响因子：
5.2
通讯作者：
Hofmann, Marie-Claude
中科院分区：
文献类型：
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作者：
Simon, Liz;Ekman, Gail C.;Garcia, Thomas;Carnes, Kay;Zhang, Zhen;Murphy, Theresa;Murphy, Kenneth M.;Hess, Rex A.;Cooke, Paul S.;Hofmann, Marie-Claude
精原干细胞是体内唯一将遗传信息传递给后代的干细胞。尽管负责这些细胞自我更新的生长因子是已知的，但吸引和物理维持这些细胞在其微环境中的因素和机制却知之甚少。靶向破坏 Ets 变异基因 5 (Etv5) 的小鼠在第一波精子发生后表现出干/祖精原细胞完全丧失，导致仅支持细胞表型和无精症。对 Etv5 敲除 (Etv5−/−) 小鼠和野生型 (WT) 小鼠的原代支持细胞进行微阵列分析，结果显示几种趋化因子的表达显着降低。趋化性测定表明，与向WT支持细胞的迁移相比，干/祖精原细胞向Etv5−/−支持细胞的迁移显着减少。有趣的是，分化的精原细胞、精母细胞和圆形精子细胞不被WT支持细胞趋化，而干/祖精原细胞表现出高且显着的趋化指数。使用重组趋化因子的救援试验表明，C-C 基序配体 9 (CCL9) 促进表达 1 型 C-C 受体 (CCR1) 的干/祖精原细胞的支持细胞化学吸引。此外，ETV5 和 Ccl9 之间存在蛋白质-DNA 相互作用，表明 ETV5 可能是 Ccl9 表达的直接调节因子。总而言之，我们的数据首次表明支持细胞对干/祖精原细胞具有化学吸引力，并且特定趋化因子的产生受到 ETV5 的调节。因此，趋化因子产生的变化以及随之而来的 Etv5−/− 支持细胞化学吸引的减少有助于解释 Etv5−/− 小鼠中干/祖精原细胞的损失。
Spermatogonial stem cells are the only stem cells in the body that transmit genetic information to offspring. Although growth factors responsible for self–renewal of these cells are known, the factors and mechanisms that attract and physically maintain these cells within their microenvironment are poorly understood. Mice with targeted disruption of Ets variant gene 5 (Etv5) show total loss of stem/progenitor spermatogonia following the first wave of spermatogenesis, resulting in a Sertoli cell–only phenotype and aspermia. Microarray analysis of primary Sertoli cells from Etv5 knockout (Etv5−/−) versus wild–type (WT) mice revealed significant decreases in expression of several chemokines. Chemotaxis assays demonstrated that migration of stem/progenitor spermatogonia toward Etv5−/− Sertoli cells was significantly decreased compared to migration toward WT Sertoli cells. Interestingly, differentiating spermatogonia, spermatocytes, and round spermatids were not chemoattracted by WT Sertoli cells, whereas stem/progenitor spermatogonia showed a high and significant chemotactic index. Rescue assays using recombinant chemokines indicated that C-C-motif ligand 9 (CCL9) facilitates Sertoli cell chemoattraction of stem/progenitor spermatogonia, which express C-C-receptor type 1 (CCR1). In addition, there is protein–DNA interaction between ETV5 and Ccl9, suggesting that ETV5 might be a direct regulator of Ccl9 expression. Taken together, our data show for the first time that Sertoli cells are chemoattractive for stem/progenitor spermatogonia, and that production of specific chemokines is regulated by ETV5. Therefore, changes in chemokine production and consequent decreases in chemoattraction by Etv5−/− Sertoli cells helps to explain stem/progenitor spermatogonia loss in Etv5−/− mice.
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影响因子：
5.2
作者：
He, Zuping;Jiang, Jiji;Kokkinaki, Maria;Dym, Martin
通讯作者：
Dym, Martin
影响因子：
3.6
作者：
DYM, M;JIA, MC;RAVINDRANATH, N
通讯作者：
RAVINDRANATH, N
DOI：
10.1007/bf02629090
发表时间：
1988-06-01
期刊：
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY
影响因子：
--
作者：
HADLEY, MA;BYERS, SW;DYM, M
通讯作者：
DYM, M
影响因子：
6.7
作者：
Colditz, Ian G.;Schneider, Martin A.;Rot, Antal
通讯作者：
Rot, Antal
影响因子：
3.6
作者：
Buageaw, A;Sukhwani, M;Schlatt, S
通讯作者：
Schlatt, S