Zebrafish Müller glia-derived progenitors are multipotent, exhibit proliferative biases and regenerate excess neurons.
Zebrafish Müller glia-derived progenitors are multipotent, exhibit proliferative biases and regenerate excess neurons.
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斑马鱼müller神经胶质衍生的祖细胞是多能，表现出增殖偏见和再生过多的神经元。
DOI：
10.1038/srep24851
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发表时间：
2016-04-20
影响因子：
4.6
通讯作者：
Goldman D
中科院分区：
文献类型：
--
作者：
Powell C;Cornblath E;Elsaeidi F;Wan J;Goldman D
与哺乳动物不同，斑马鱼可以再生受损的视网膜。这种再生反应的关键是Müller胶质细胞（MG），它通过重新编程和采用视网膜干细胞特性来对损伤做出反应。这些重编程的MG分裂产生增殖的视网膜祖细胞群，其迁移到视网膜损伤区域并再生丢失的神经元。以前的研究表明，MG衍生的祖细胞可能偏向于产生随着损伤而丢失的祖细胞。在这里，我们研究了MG多能性使用损伤范例，靶向不同的视网膜核层的细胞消融。我们的数据表明，无论哪个核层受损，MG通过产生多能祖细胞来响应，所述多能祖细胞迁移到所有核层并分化成层特异性细胞类型，这表明受损视网膜中的MG衍生祖细胞本质上是多能的。然而，我们对祖细胞增殖的分析揭示了在神经元被消融的核层中的增殖优势。这表明来自存活神经元的反馈抑制可能使神经元再生偏向消融的细胞类型。
Unlike mammals, zebrafish can regenerate a damaged retina. Key to this regenerative response are Müller glia (MG) that respond to injury by reprogramming and adopting retinal stem cell properties. These reprogrammed MG divide to produce a proliferating population of retinal progenitors that migrate to areas of retinal damage and regenerate lost neurons. Previous studies have suggested that MG-derived progenitors may be biased to produce that are lost with injury. Here we investigated MG multipotency using injury paradigms that target different retinal nuclear layers for cell ablation. Our data indicate that regardless of which nuclear layer was damaged, MG respond by generating multipotent progenitors that migrate to all nuclear layers and differentiate into layer-specific cell types, suggesting that MG-derived progenitors in the injured retina are intrinsically multipotent. However, our analysis of progenitor proliferation reveals a proliferative advantage in nuclear layers where neurons were ablated. This suggests that feedback inhibition from surviving neurons may skew neuronal regeneration towards ablated cell types.