ArticleNature communications2025
Chemical reprogramming of fibroblasts into retinal pigment epithelium cells for vision restoration.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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18 authors.
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Abstract
Restoring retinal pigment epithelium (RPE) cells is crucial for treating retinal degenerative (RD) diseases, with chemical reprogramming offering a transformative, scalable solution. However, identifying key chemical compounds for generating functional RPE cells from somatic cells remains challenging. Here, we present a two-step chemical reprogramming strategy to convert fibroblasts into functional chemical induced RPE (ciRPE) cells. Leveraging the Single-Cell Reprogramming Compound Finder (scRCF), which integrates transcriptomics-guided predictions with advanced screening, we identified chemical cocktails that precisely reprogram fibroblasts through an intermediate state into ciRPE cells. These ciRPE cells closely mimic the structure and function of native RPE cells, and upon transplantation into RD rats, they seamlessly integrate into host tissue, protect photoreceptors, and restore visual function. Omics and mechanistic analyses revealed that the identified compounds synergistically activate core transcription factors, including Ascl1 and Olig2, orchestrating the reprogramming process. This study provides a scalable, non-integrative approach for generating functional RPE cells, offering a promising strategy for cell replacement therapies targeting RD diseases.
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