The purpose of this study was to investigate how ID factors regulate the ability of Müller glia (MG) to reprogram into proliferating MG‐derived progenitor cells (MGPCs) in the chick retina. We found that ID1 is transiently expressed by maturing MG (mMG), whereas ID4 is maintained in mMG in embryonic retinas. In mature retinas, ID4 was prominently expressed by resting MG, but following retinal damage ID4 was rapidly upregulated and then downregulated in MGPCs. By contrast, ID1, ID2, and ID3 were low in resting MG and then upregulated in MGPCs. Inhibition of ID factors following retinal damage decreased numbers of proliferating MGPCs. Inhibition of IDs, after MGPC proliferation, significantly increased numbers of progeny that differentiated as neurons. In damaged or undamaged retinas inhibition of IDs increased levels of p21Cip1 in MG. In response to damage or insulin+FGF2 levels of CDKN1A message and p21Cip1 protein were decreased, absent in proliferating MGPCs, and elevated in MG returning to a resting phenotype. Inhibition of notch‐ or gp130/Jak/Stat‐signaling in damaged retinas increased levels of ID4 but not p21Cip1 in MG. Although ID4 is the predominant isoform expressed by MG in the chick retina, id1 and id2a are predominantly expressed by resting MG and downregulated in activated MG and MGPCs in zebrafish retinas. We conclude that ID factors have a significant impact on regulating the responses of MG to retinal damage, controlling the ability of MG to proliferate by regulating levels of p21Cip1, and suppressing the neurogenic potential of MGPCs.

中文翻译：

---

ID因子调节Müller胶质细胞成为增殖性神经源性祖细胞样细胞的能力

本研究的目的是研究 ID 因子如何调节 Müller 胶质细胞 (MG) 重编程为小鸡视网膜中增殖的 MG 衍生祖细胞 (MGPC) 的能力。我们发现识别号1由成熟的 MG (mMG) 瞬时表达，而ID4维持在胚胎视网膜中的 mMG 中。在成熟的视网膜中，ID4在静息 MG 时显着表达，但在视网膜损伤后ID4在 MGPC 中快速上调然后下调。相比之下，识别号1,识别号2， 和ID3静息 MG 中较低，然后 MGPC 中上调。视网膜损伤后抑制 ID 因子可减少增殖的 MGPC 数量。 MGPC 增殖后，ID 的抑制显着增加了分化为神经元的后代数量。在受损或未受损的视网膜中，抑制 IDs 会增加 p21 的水平Cip1在MG。响应损伤或胰岛素+FGF2水平CDKN1A消息和p21Cip1蛋白质减少，在增殖的 MGPC 中不存在，而在 MG 恢复静息表型时蛋白质增加。抑制受损视网膜中的 notch 或 gp130/Jak/Stat 信号传导会增加ID4但不是p21Cip1在MG。虽然ID4是 MG 在小鸡视网膜中表达的主要亚型，编号1和id2a主要由静息 MG 表达，并在斑马鱼视网膜的激活 MG 和 MGPC 中下调。我们得出结论，ID因素对调节MG对视网膜损伤的反应具有显着影响，通过调节p21的水平来控制MG增殖的能力Cip1，并抑制 MGPC 的神经源性潜力。