Abstract：
In the injured zebrafish retina, Müller glial cells (MG) reprogram to adopt retinal stem cell properties and regenerate damaged neurons. The strongest zebrafish reprogramming factors might be good candidates for stimulating a similar regenerative response by mammalian MG. Myc proteins are potent reprogramming factors that can stimulate cellular plasticity in differentiated cells; however, their role in MG reprogramming and retina regeneration remains poorly explored. Here, we report that retinal injury stimulates mycb and mych expression and that, although both Mycb and Mych stimulate MG reprogramming and proliferation, only Mych enhances retinal neuron apoptosis. RNA-sequencing analysis of wild-type, mychmut and mycbmut fish revealed that Mycb and Mych regulate ∼40% and ∼16%, respectively, of the genes contributing to the regeneration-associated transcriptome of MG. Of these genes, those that are induced are biased towards regulation of ribosome biogenesis, protein synthesis, DNA synthesis, and cell division, which are the top cellular processes affected by retinal injury, suggesting that Mycb and Mych are potent MG reprogramming factors. Consistent with this, forced expression of either of these proteins is sufficient to stimulate MG proliferation in the uninjured retina.
摘要：
在受伤的斑马鱼视网膜中，Müller胶质细胞（MG）重新编程以采用视网膜干细胞特性并再生受损的神经元。最强的斑马鱼重编程因子可能是刺激哺乳动物MG类似再生反应的良好候选者。Myc蛋白是有效的重编程因子，可以刺激分化细胞的细胞可塑性；然而，它们在MG重编程和视网膜再生中的作用尚不清楚。在这里，我们报道了视网膜损伤刺激mycb和mych表达，尽管Mycb和Mych都刺激MG重编程和增殖，只有Mych增强视网膜神经元凋亡。Wt的RNAseq分析，mychmut,Mycbmut鱼显示Mycb和Mych调节40%和16%，分别,有助于MG再生相关转录组的基因。在这些基因中，那些被诱导的偏向于调节核糖体生物发生，蛋白质合成，DNA合成，和细胞分裂是受视网膜损伤调节的顶级细胞过程，这表明Mycb和Mych是有效的MG重编程因子。与此一致，这些蛋白质中的任一种的强制表达足以刺激未损伤的视网膜中的MG增殖。
