Inducing human retinal pigment epithelium-like cells from somatic tissue
Ivo Ngundu Woogeng, Bogumił 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
Abstract
Regenerative medicine relies on basic research outcomes that are only practical when cost effective. The human eyeball requires the retinal pigment epithelium (RPE) to interface the neural retina and the choroid at large. Millions of people suffer from age-related macular degeneration (AMD), a blinding multifactor genetic disease among RPE degradation pathologies. Recently, autologous pluripotent stem-cell-derived RPE cells were prohibitively expensive due to time; therefore, we developed a faster reprogramming system. We stably induced RPE-like cells (iRPE) from human fibroblasts (Fibs) by conditional overexpression of both broad plasticity and lineage-specific transcription factors (TFs). iRPE cells displayed critical RPE benchmarks and significant in vivo integration in transplanted retinas. Herein, we detail the iRPE system with comprehensive single-cell RNA sequencing (scRNA-seq) profiling to interpret and characterize its best cells. We anticipate that our system may enable robust retinal cell induction for basic research and affordable autologous human RPE tissue for regenerative cell therapy.