Taylor Olivia B, El-Hodiri Heithem M, Palazzo Isabella, Todd Levi, Fischer Andy J
Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Neuroscience Graduate Program, The Ohio State University, Columbus, Ohio, USA.
Glia. 2025 Jan;73(1):4-24. doi: 10.1002/glia.24635. Epub 2024 Oct 24.
We summarize recent findings in different animal models regarding the different cell-signaling pathways and gene networks that influence the reprogramming of Müller glia into proliferating, neurogenic progenitor cells in the retina. Not surprisingly, most of the cell-signaling pathways that guide the proliferation and differentiation of embryonic retinal progenitors also influence the ability of Müller glia to become proliferating Müller glia-derived progenitor cells (MGPCs). Further, the neuronal differentiation of MGPC progeny is potently inhibited by networks of neurogenesis-suppressing genes in chick and mouse models but occurs freely in zebrafish. There are important differences between the model systems, particularly pro-inflammatory signals that are active in mature Müller glia in damaged rodent and chick retinas, but less so in fish retinas. These pro-inflammatory signals are required to initiate the process of reprogramming, but if sustained suppress the potential of Müller glia to become neurogenic MGPCs. Further, there are important differences in how activated Müller glia up- or downregulate pro-glial transcription factors in the different model systems. We review recent findings regarding regulatory cell signaling and gene networks that influence the activation of Müller glia and the transition of these glia into proliferating progenitor cells with neurogenic potential in fish, chick, and mouse model systems.
我们总结了近期在不同动物模型中的研究结果，这些结果涉及影响穆勒胶质细胞重编程为视网膜中增殖性神经源性祖细胞的不同细胞信号通路和基因网络。不出所料，大多数指导胚胎视网膜祖细胞增殖和分化的细胞信号通路，也会影响穆勒胶质细胞转变为增殖性穆勒胶质细胞衍生祖细胞（MGPCs）的能力。此外，在鸡和小鼠模型中，神经发生抑制基因网络强烈抑制MGPC后代的神经元分化，但在斑马鱼中则可自由发生。模型系统之间存在重要差异，特别是在受损啮齿动物和鸡视网膜的成熟穆勒胶质细胞中活跃的促炎信号，在鱼类视网膜中则不那么活跃。这些促炎信号是启动重编程过程所必需的，但如果持续存在，则会抑制穆勒胶质细胞成为神经源性MGPCs的潜能。此外，在不同模型系统中，被激活的穆勒胶质细胞上调或下调促胶质转录因子的方式也存在重要差异。我们回顾了近期关于调节细胞信号和基因网络的研究结果，这些网络影响穆勒胶质细胞的激活以及这些胶质细胞在鱼类、鸡和小鼠模型系统中转变为具有神经源性潜能的增殖祖细胞的过程。
