Ephrin-A3 suppresses Wnt signaling to control retinal stem cell potency.
Ephrin-A3 suppresses Wnt signaling to control retinal stem cell potency.
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DOI：
10.1002/stem.1283
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发表时间：
2013-02
期刊：
影响因子：
5.2
通讯作者：
Chen, Dong Feng
中科院分区：
文献类型：
--
作者：
Fang, Yuan;Cho, Kin-Sang;Tchedre, Kissaou;Lee, Seung Woo;Guo, Chenying;Kinouchi, Hikaru;Fried, Shelley;Sun, Xinghuai;Chen, Dong Feng
据报道，成年哺乳动物的睫状体上皮(CE)提供了视网膜干细胞(RSCs)的来源，在体外可以分化出所有类型的视网膜细胞。然而，最近的一项研究表明，CE来源的细胞具有有色睫状体上皮细胞的特性，并且几乎没有神经发生的潜力。在这里，我们表明CE来源的细胞的神经分化潜能受到eaffin-A3的负性调节，它在出生后小鼠的CE中上调，并为成年RSCs提供了一个强大的禁止性生态位。加入肾上腺素-A3可抑制CE来源的RSCs的增殖，增加色素上皮细胞的命运。相反，缺乏eaffin-A3促进增殖并增加神经前体细胞标记物和光感受器后代的表达。EphA3对CE来源的RSCs的负性作用是通过激活EphA4受体和抑制WNT3a/β-catenin信号转导而实现的。综上所述，我们的数据表明，CE来源的RSCs包含产生光感受器和其他视网膜神经元的内在机制，而成年小鼠的CE表达负调控因子，阻止RSCs的增殖和神经分化。因此，操控肾上腺素和Wnt/β-catenin信号通路可能是激活CE来源的RSCs内源性神经源性潜能的可行途径，用于治疗光感受器损伤和视网膜退行性疾病。
The ciliary epithelium (CE) of adult mammals has been reported to provide a source of retinal stem cells (RSCs) that can give rise to all retinal cell types in vitro. A recent study, however, suggests that CE-derived cells possess properties of pigmented ciliary epithelial cells and display little neurogenic potential. Here we show that the neurogenic potential of CE-derived cells is negatively regulated by ephrin-A3, which is upregulated in the CE of postnatal mice and presents a strong prohibitory niche for adult RSCs. Addition of ephrin-A3 inhibits proliferation of CE-derived RSCs and increases pigment epithelial cell fate. In contrast, absence of ephrin-A3 promotes proliferation and increases expression of neural progenitor cell markers and photoreceptor progeny. The negative effects of ephrin-A3 on CE-derived RSCs are mediated through activation of an EphA4 receptor and suppression of Wnt3a/β-catenin signaling. Together, our data suggest that CE-derived RSCs contain the intrinsic machinery to generate photoreceptors and other retinal neurons, while the CE of adult mice expresses negative regulators that prohibit the proliferation and neural differentiation of RSCs. Manipulating ephrin and Wnt/β-catenin signaling may, thus, represents a viable approach to activating the endogenous neurogenic potential of CE-derived RSCs for treating photoreceptor damage and retinal degenerative disorders.
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DOI：
10.1073/pnas.0401596101
发表时间：
2004-11-02
影响因子：
11.1
作者：
Coles, BLK;Angénieux, B;van der Kooy, D
通讯作者：
van der Kooy, D
影响因子：
5.2
作者：
MacNeil, Angus;Pearson, Rachael A.;Ali, Robin R.
通讯作者：
Ali, Robin R.
影响因子：
5.2
作者：
Inoue, Tomoyuki;Coles, Brenda L. K.;Dorval, Kim;Bremner, Rod;Bessho, Yasumasa;Kageyama, Ryoichiro;Hino, Shinjiro;Matsuoka, Masao;Craft, Cheryl M.;McInnes, Roderick R.;Tremblay, Francois;Prusky, Glen T.;van der Kooy, Derek
通讯作者：
van der Kooy, Derek
影响因子：
3.4
作者：
Abdouh, Mohamed;Bernier, Gilbert
通讯作者：
Bernier, Gilbert
影响因子：
2.5
作者：
Fried, Shelley I.;Lasker, Aaron C. W.;Rizzo, Joseph F., III
通讯作者：
Rizzo, Joseph F., III