美国约翰•霍普金斯大学Seth Blackshaw、Jiang Qian和圣母大学David R. Hyde课题组合作的最新研究，揭示了控制脊椎动物视网膜再生的基因调控网络。相关论文于2020年10月1日发表在《科学》杂志上。

为了揭示Müller胶质细胞重编程为祖细胞的基因调控网络，研究人员对斑马鱼、小鸡和小鼠Müller胶质细胞中基因表达和染色质可及性的响应变化进行了分析。研究人员确定了进化上保守以及物种特异的基因网络，它们控制神经胶质的静息、反应性和神经发生。

在斑马鱼和小鸡中，从静息到反应性的过渡对于视网膜再生至关重要；而在小鼠中，专用网络抑制神经原反应能力并恢复静息。维持并恢复静息状态的核因子I（NFI）转录因子的破坏，导致成年小鼠受伤后Müller胶质细胞增殖并产生神经元。这些发现可能有助于恢复因变性疾病而丧失视网膜神经元疗法的发展。

据了解，损伤会引起某些冷血脊椎动物（而非哺乳动物）视网膜Müller胶质细胞再生为神经元。

附：英文原文

Title: Gene regulatory networks controlling vertebrate retinal regeneration

Author: Thanh Hoang, Jie Wang, Patrick Boyd, Fang Wang, Clayton Santiago, Lizhi Jiang, Sooyeon Yoo, Manuela Lahne, Levi J. Todd, Meng Jia, Cristian Saez, Casey Keuthan, Isabella Palazzo, Natalie Squires, Warren A. Campbell, Fatemeh Rajaii, Trisha Parayil, Vickie Trinh, Dong Won Kim, Guohua Wang, Leah J. Campbell, John Ash, Andy J. Fischer, David R. Hyde, Jiang Qian, Seth Blackshaw

Issue&Volume: 2020/10/01

Abstract: Injury induces retinal Müller glia of certain cold-blooded vertebrates, but not mammals, to regenerate neurons. To identify gene regulatory networks that reprogram Müller glia into progenitor cells, we profiled changes in gene expression and chromatin accessibility in Müller glia from zebrafish, chick and mice in response to different stimuli. We identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, reactivity and neurogenesis. In zebrafish and chick, transition from the quiescence to reactivity is essential for retinal regeneration, while in mice a dedicated network suppresses neurogenic competence and restores quiescence. Disruption of nuclear factor I (NFI) transcription factors, which maintain and restore quiescence, induces Müller glia to proliferate and generate neurons in adult mice following injury. These findings may aid in designing therapies to restore retinal neurons lost to degenerative diseases.

DOI: 10.1126/science.abb8598

Source: https://science.sciencemag.org/content/early/2020/09/30/science.abb8598