MEK/ERK signaling directly and indirectly contributes to the cyclical self-renewal of spermatogonial stem cells.
MEK/ERK signaling directly and indirectly contributes to the cyclical self-renewal of spermatogonial stem cells.
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DOI：
10.1002/stem.1486
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发表时间：
2013-11
期刊：
影响因子：
5.2
通讯作者：
Saga, Yumiko
中科院分区：
文献类型：
--
作者：
Hasegawa, Kazuteru;Namekawa, Satoshi H.;Saga, Yumiko
干细胞命运的协调受外在的生态位信号和干细胞内在因素的调节。在哺乳动物的睾丸中，精原干细胞根据一个被称为生精上皮周期的周期性程序，定期在自我更新和分化之间交替，从而维持丰富精子的持续产生。尽管维甲酸(RA)信号被认为可以指导精原干细胞的周期分化，但其依赖于周期的自我更新/增殖是如何调控的，目前还不清楚。在这里，我们证明了MEK/ERK信号对精原干细胞的周期活动有贡献。我们发现，在支持细胞的自我更新/增殖阶段，ERK1/2被周期性地激活，而关键的生态位因子GDNF的阶段相关表达需要MEK/ERK信号。此外，在胶质细胞源性神经营养因子的控制下，GFRα1阳性的精原干细胞中ERK1/2被激活，并阻止它们分化。这些结果表明，MEK/ERK信号通过介导促进精原干细胞周期性自我更新/增殖的信号，直接和间接地维持精原干细胞。反之，RA信号直接或间接诱导精原干细胞分化。我们认为，时间调节的RA信号的激活和调节MEK/ERK的信号拮抗地协调精原干细胞的周期相关活动。
Coordination of stem cell fate is regulated by extrinsic niche signals and stem cell intrinsic factors. In mammalian testes, spermatogonial stem cells maintain constant production of abundant spermatozoa by alternating between self-renewal and differentiation at regular intervals according to a periodical program known as the seminiferous epithelial cycle. Although retinoic acid (RA) signaling has been suggested to direct the cyclical differentiation of spermatogonial stem cells, it remains largely unclear how their cycle-dependent self-renewal/proliferation is regulated. Here, we show that MEK/ERK signaling contributes to the cyclical activity of spermatogonial stem cells. We found that ERK1/2 are periodically activated in Sertoli cells during the stem cell self-renewal/proliferation phase, and that MEK/ERK signaling is required for the stage-related expression of the critical niche factor GDNF. In addition, ERK1/2 are activated in GFRα1-positive spermatogonial stem cells under the control of GDNF and prevent them from being differentiated. These results suggest that MEK/ERK signaling directly and indirectly maintains spermatogonial stem cells by mediating a signal that promotes their periodical self-renewal/proliferation. Conversely, RA signaling directly and indirectly induces differentiation of spermatogonial stem cells. We propose that temporally-regulated activations of RA signaling and a signal regulating MEK/ERK antagonistically coordinates the cycle-related activity of spermatogonial stem cells.
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影响因子：
3.7
作者：
Sato T;Aiyama Y;Ishii-Inagaki M;Hara K;Tsunekawa N;Harikae K;Uemura-Kamata M;Shinomura M;Zhu XB;Maeda S;Kuwahara-Otani S;Kudo A;Kawakami H;Kanai-Azuma M;Fujiwara M;Miyamae Y;Yoshida S;Seki M;Kurohmaru M;Kanai Y
通讯作者：
Kanai Y
影响因子：
2.5
作者：
De Rooij, Dirk G.
通讯作者：
De Rooij, Dirk G.
影响因子：
3.7
作者：
Simon, Liz;Ekman, Gail C.;Cooke, Paul S.
通讯作者：
Cooke, Paul S.
DOI：
10.1126/science.1218835
发表时间：
2012-08-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Doupé DP;Alcolea MP;Roshan A;Zhang G;Klein AM;Simons BD;Jones PH
通讯作者：
Jones PH
影响因子：
11.8
作者：
Nakagawa, Toshinori;Nabeshima, Yo-ichi;Yoshida, Shosei
通讯作者：
Yoshida, Shosei