视网膜Muller细胞调控感光细胞成熟的分子机制

干细胞移植是治疗视网膜变性疾病的潜在疗法，然而，如何获得感光前体细胞以及精准调控其成熟、功能整合是目前需解决的关键问题。课题组通过单细胞转录组测序hESCs 来源视网膜类器官，鉴定出感光祖细胞表面标记物--KCNH2，还发现Muller细胞通过Pleiothropin (PTN)-protein tyrosine phosphatase receptor type Z1 (PTPRZ1) 调控感光祖细胞发育成熟，然而其调控感光细胞成熟的机制尚不清楚。因此，本课题拟通过单细胞多组学研究hESCs三维培养定向诱导分化来源Muller细胞及PPCs的细胞群，分析转录组、染色质易接近性的动态特征，解析Muller细胞调控感光祖细胞的分子机制，并通过ChIP-Seq确定特定调控因子的靶基因，绘制出PPCs细胞群的分化发育树；改善视网膜变性动物的Muller细胞活性，实现在体调控移植感光祖细胞成熟。

Transplant of stem cell is promising for cure retinal degeneration disease, however, the acquirement of photoreceptor progenitor cells(PPCs) and precisely control its maturation in vivo is challenging. In our primary work, we isolated PPCs by the new marker gene--KCNH2 and found interaction between Müller cell and PPCs through PTN-PTPRZ1. But how does Muller cell regulate PPCs maturation is still unknown. In our future work, we intend to explore the molecular character of Muller and PPCs through single cell multimodal-omics analysis, and present the molecular mechanism of Muller cell regulating PPCs maturation. According to this, we could modify the character the Muller cell in degenerating retina and improve the integration of PPCs.