Inducing human retinal pigment epithelium-like cells from somatic tissue

• DOI: 10.1016/j.stemcr.2021.12.008
• Publication Date: 2022-01-13T15:35:42Z
• Authors: Ivo Ngundu Woogeng; Bogumil Kaczkowski; Imad Abugessaisa; Haiming Hu; Akihiro Tachibana; Yoshiki Sahara; Chung-Chau Hon; Akira Hasegawa; Noriko Sakai; Mitsuhiro Nishida; Hashimita Sanyal; Junki Sho; Keisuke Kajita; Takeya Kasukawa; Minoru Takasato; Piero Carninci; Akiko Maeda; Michiko Mandai; Erik Arner; Masayo Takahashi; Cody Kime
• Keywords: Niacinamide; 0303 health sciences; Retinal Pigment Epithelium; Fibroblasts; Cellular Reprogramming; Article; Retina; Indole Alkaloids; Rats; 3. Good health; Machine Learning; 03 medical and health sciences; Gene Expression Regulation; Animals; Humans; Disulfides; Transcription Factors

SUMMARYRegenerative medicine relies on basic research to find safe and useful outcomes that are only practical when cost-effective. The human eyeball requires the retinal pigment epithelium (RPE) for support and maintenance that interfaces the neural retina and the choroid at large. Nearly 200 million people suffer from age-related macular degeneration (AMD), a blinding multifactor genetic disease among other retinal pathologies related to RPE degradation. Recently, autologous pluripotent stem cell-derived RPE cells were prohibitively expensive due totime,therefore we developed a new simplified cell reprogramming system. We stably induced RPE-like cells (iRPE) from human fibroblasts by conditional overexpression of broad plasticity and lineage-specific pioneering transcription factors. iRPE cells showed features of modern RPE benchmarks and significantin-vivointegration in transplanted chimeric hosts. Herein, we detail the iRPE system with comprehensive modern single-cell RNA (scRNA) sequencing profiling to interpret and characterize its best cells. We anticipate that our system may enable robust retinal cell induction for regenerative medicine research and affordable autologous human RPE tissue for cell therapy.