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| Global Transcriptional and Epigenetic Reconfiguration during Chemical Reprogramming of Human Retinal Pigment Epithelial Cells into Photoreceptor-like Cells | |
| 2022-10 | |
| Source Publication | CELLS
 |
| EISSN | 2073-4409 |
| Volume | 11Issue:19 |
| Status | 已发表 |
| DOI | 10.3390/cells11193146 |
| Abstract | Retinal degenerative diseases are frequently caused by the loss of retinal neural cells such as photoreceptors. Cell replacement is regarded as one of the most promising therapies. Multiple types of stem and somatic cells have been tested for photoreceptor conversion. However, current induction efficiencies are still low and the molecular mechanisms underlying reprogramming remain to be clarified. In this work, by combining treatment with small molecules, we directly reprogrammed human fetal retinal pigment epithelial (RPE) cells into chemically induced photoreceptor-like cells (CiPCs) in vitro. Bulk and single-cell RNA sequencing, as well as methylation sequencing, were performed to understand the transcriptional and epigenetic changes during CiPCs conversion. A multi-omics analysis showed that the direct reprogramming process partly resembled events of early retina development. We also found that the efficiency of CiPCs conversion from RPE is much better than that from human dermal fibroblasts (HDF). The small molecules effectively induced RPE cells into CiPCs via suppression of the epithelial-to-mesenchymal transition (EMT). Among the signaling pathways involved in CiPCs conversion, glutamate receptor activation is prominent. In summary, RPE cells can be efficiently reprogrammed into photoreceptor-like cells through defined pharmacological modulations, providing a useful cell source for photoreceptor generation in cell replacement therapy for retinal degenerative diseases. |
| Keyword | human retinal pigment epithelial cells photoreceptor-like cells chemical reprogramming single-cell RNA sequencing DNA methylation sequencing |
| URL | 查看原文 |
| Indexed By | SCI ; SCIE |
| Language | 英语 |
| Funding Project | National Natural Science Foundation of China (NSFC)[31871288] |
| WOS Research Area | Cell Biology |
| WOS Subject | Cell Biology |
| WOS ID | WOS:000866749600001 |
| Publisher | MDPI |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/240484 |
| Collection | 免疫化学研究所_特聘教授组_范国平组 |
| Corresponding Author | Wang, Jing; Liu, Yizhi; Fan, Guoping |
| Affiliation | 1.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou 510060, Peoples R China 2.Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA 3.Univ Calif San Diego, Dept NanoEngn, La Jolla, CA 92093 USA 4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China |
| Corresponding Author Affilication | Shanghai Institute for Advanced Immunochemical Studies |
| Recommended Citation GB/T 7714 | Deng, Xiaoqian,Lee, Ryan,Lim, Sin Yee,et al. Global Transcriptional and Epigenetic Reconfiguration during Chemical Reprogramming of Human Retinal Pigment Epithelial Cells into Photoreceptor-like Cells[J]. CELLS,2022,11(19). |
| APA | Deng, Xiaoqian.,Lee, Ryan.,Lim, Sin Yee.,Zhong, Zheng.,Wang, Jing.,...&Fan, Guoping.(2022).Global Transcriptional and Epigenetic Reconfiguration during Chemical Reprogramming of Human Retinal Pigment Epithelial Cells into Photoreceptor-like Cells.CELLS,11(19). |
| MLA | Deng, Xiaoqian,et al."Global Transcriptional and Epigenetic Reconfiguration during Chemical Reprogramming of Human Retinal Pigment Epithelial Cells into Photoreceptor-like Cells".CELLS 11.19(2022). |
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