Induced retinal pigment epithelial cells with anti-epithelial-to-mesenchymal transition ability delay retinal degeneration
Summary: 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...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222013220 |
| _version_ | 1811204377552093184 |
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| author | Haibin Tian Zhiyang Chen Xiaoman Zhu Qingjian Ou Zhe Wang Binxin Wu Jing-Ying Xu Caixia Jin Furong Gao Juan Wang Jingfa Zhang Jieping Zhang Lixia Lu Guo-Tong Xu |
| author_facet | Haibin Tian Zhiyang Chen Xiaoman Zhu Qingjian Ou Zhe Wang Binxin Wu Jing-Ying Xu Caixia Jin Furong Gao Juan Wang Jingfa Zhang Jieping Zhang Lixia Lu Guo-Tong Xu |
| author_sort | Haibin Tian |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-12T03:12:16Z |
| format | Article |
| id | doaj.art-6e289ac5e44c4b91aae4ab9f6b7d76c9 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-12T03:12:16Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-6e289ac5e44c4b91aae4ab9f6b7d76c92022-12-22T03:50:19ZengElsevieriScience2589-00422022-10-012510105050Induced retinal pigment epithelial cells with anti-epithelial-to-mesenchymal transition ability delay retinal degenerationHaibin Tian0Zhiyang Chen1Xiaoman Zhu2Qingjian Ou3Zhe Wang4Binxin Wu5Jing-Ying Xu6Caixia Jin7Furong Gao8Juan Wang9Jingfa Zhang10Jieping Zhang11Lixia Lu12Guo-Tong Xu13Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China; Corresponding authorDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University, Shanghai 200080, ChinaDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, ChinaDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China; Corresponding authorDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China; Department of Physiology and Pharmacology, Tongji University School of Medicine, Shanghai 200092, China; The collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004222013220Biological sciencesMolecular biologyStem cells research |
| spellingShingle | Haibin Tian Zhiyang Chen Xiaoman Zhu Qingjian Ou Zhe Wang Binxin Wu Jing-Ying Xu Caixia Jin Furong Gao Juan Wang Jingfa Zhang Jieping Zhang Lixia Lu Guo-Tong Xu Induced retinal pigment epithelial cells with anti-epithelial-to-mesenchymal transition ability delay retinal degeneration iScience Biological sciences Molecular biology Stem cells research |
| title | Induced retinal pigment epithelial cells with anti-epithelial-to-mesenchymal transition ability delay retinal degeneration |
| title_full | Induced retinal pigment epithelial cells with anti-epithelial-to-mesenchymal transition ability delay retinal degeneration |
| title_fullStr | Induced retinal pigment epithelial cells with anti-epithelial-to-mesenchymal transition ability delay retinal degeneration |
| title_full_unstemmed | Induced retinal pigment epithelial cells with anti-epithelial-to-mesenchymal transition ability delay retinal degeneration |
| title_short | Induced retinal pigment epithelial cells with anti-epithelial-to-mesenchymal transition ability delay retinal degeneration |
| title_sort | induced retinal pigment epithelial cells with anti epithelial to mesenchymal transition ability delay retinal degeneration |
| topic | Biological sciences Molecular biology Stem cells research |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222013220 |
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