上皮-间质转换
诱导多能干细胞
细胞生物学
视网膜色素上皮
视网膜
黄斑变性
视网膜
小眼畸形相关转录因子
视网膜再生
化学
癌症研究
间充质干细胞
生物
转录因子
下调和上调
再生(生物学)
胚胎干细胞
生物化学
医学
神经科学
基因
眼科
作者
Haibin Tian,Ziyang Chen,Xiaoman Zhu,Qingjian Ou,Zhe Wang,Binxin Wu,Jingying Xu,Can Jin,Furong Gao,Juan Wang,Jingfa Zhang,Jieping Zhang,Lixia Lü,Guo‐Tong Xu
出处
期刊:iScience
[Elsevier]
日期:2022-10-01
卷期号:25 (10): 105050-105050
被引量:1
标识
DOI:10.1016/j.isci.2022.105050
摘要
The hostile microenvironment of the retina in patients with age-related macular degeneration (AMD) may trigger epithelial-to-mesenchymal transition (EMT) of grafted retinal pigment epithelial (RPE) cells, thus attenuating the therapeutic outcome. Here, we transformed human dedifferentiated induced pluripotent stem cell-derived RPE (iPSC-RPE) cells into induced RPE (iRPE) cells using a cocktail of four transcription factors (TFs)-CRX, MITF-A, NR2E1, and C-MYC. These critical TFs maintained the epithelial property of iRPE cells by regulating the expression of bmp7, forkhead box f2, lin7a, and pard6b, and conferred resistance to TGF-β-induced EMT in iRPE cells by targeting ppm1a. The iRPE cells with Tet-on system-regulated c-myc expression exhibited EMT resistance and better therapeutic function compared with iPSC-RPE cells in rat AMD model. Our study demonstrates that endowing RPE cells with anti-EMT property avoids the risk of EMT after cells are grafted into the subretinal space, and it may provide a suitable candidate for AMD treatment.
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