Neural stem cell properties of Miller glia in the mammalian retina: Regulation by Notch and Wnt signaling
Neural stem cell properties of Miller glia in the mammalian retina: Regulation by Notch and Wnt signaling
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DOI：
10.1016/j.ydbio.2006.07.029
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发表时间：
2006-11-01
影响因子：
2.7
通讯作者：
Ahmad, Iqbal
中科院分区：
文献类型：
--
作者：
Das, Ani V.;Mallya, Kavita B.;Ahmad, Iqbal
与鱼类和两栖动物等低等脊椎动物不同，成年哺乳动物的视网膜不支持神经发生。然而，当成年哺乳动物的视网膜受到损伤时，会表现出神经源性的变化，这增加了神经源性潜力可能在进化上是保守的，并可以用于再生治疗的可能性。在这里，我们表明，当从正常视网膜回溯丰富的Muller细胞，就像它们在中枢神经系统(CNS)中的放射状胶质细胞一样，显示出神经干细胞(NSCs)的基本特征，即它们自我更新并生成CNS的所有三种基本细胞类型。此外，它们在体外和体内都具有生成视网膜神经元的潜力。我们还提供了直接证据，通过将预期浓缩的损伤激活的穆勒细胞移植到正常眼中，证明穆勒细胞具有神经生成潜力并可以生成视网膜神经元，证实了最初在低等脊椎动物中提出的假设。这种潜力可能是由于Muller细胞的NSC性质所致，该细胞在成人正常视网膜的非神经源性环境的约束下保持休眠。此外，我们还证明了激活Muller细胞中休眠干细胞属性的机制涉及Wnt和Notch通路。综上所述，这些结果确认Miller细胞是哺乳动物视网膜中的潜在神经干细胞，因此，可能成为治疗视网膜变性的细胞操作的潜在靶点。(C)2006 Elsevier Inc.保留所有权利。
The retina in adult mammals, unlike those in lower vertebrates such as fish and amphibians, is not known to support neurogenesis. However, when injured, the adult mammalian retina displays neurogenic changes, raising the possibility that neurogenic potential may be evolutionarily conserved and could be exploited for regenerative therapy. Here, we show that Muller cells, when retrospectively enriched from the normal retina, like their radial glial counterparts in the central nervous system (CNS), display cardinal features of neural stem cells (NSCs), i.e., they self-renew and generate all three basic cell types of the CNS. In addition, they possess the potential to generate retinal neurons, both in vitro and in vivo. We also provide direct evidence, by transplanting prospectively enriched injury-activated Muller cells into normal-eye, that Muller cells have neurogenic potential and can generate retinal neurons, confirming a hypothesis, first proposed in lower vertebrates. This potential is likely due to the NSC nature of Muller cells that remains dormant under the constraint of non-neurogenic environment of the adult normal retina. Additionally, we demonstrate that the mechanism of activating the dormant stem cell properties in Muller cells involves Wnt and Notch pathways. Together, these results identify Miller cells as latent NSCs in the mammalian retina and hence, may serve as a potential target for cellular manipulation for treating retinal degeneration. (c) 2006 Elsevier Inc. All rights reserved.