Inducing Human Retinal Pigment Epithelium-like Cells from Somatic Tissue

Woogeng, I. N.; Abugessaisa, I.; Tachibana, A.; Sahara, Y.; Hon, C.-C.; Hasegawa, A.; Kaczkowski, B.; Sakai, N.; Nishida, M.; Hu, H.; Sanyal, H.; Sho, J.; Kasukawa, T.; Takasato, M.; Carninci, P.; Maeda, A.; Mandai, M.; Arner, E.; Takahashi, M.; Kime, C.

doi:10.1101/2020.07.27.215103

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bioRxiv · 10.1101/2020.07.27.215103

Inducing Human Retinal Pigment Epithelium-like Cells from Somatic Tissue

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Abstract

Regenerative 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 to time, 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 significant in-vivo integration 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.

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Woogeng, I. N., Abugessaisa, I., Tachibana, A., Sahara, Y., Hon, C.-C., Hasegawa, A., Kaczkowski, B., Sakai, N., Nishida, M., Hu, H., Sanyal, H., Sho, J., Kasukawa, T., Takasato, M., Carninci, P., Maeda, A., Mandai, M., Arner, E., Takahashi, M., Kime, C.. 2020-07-27. Inducing Human Retinal Pigment Epithelium-like Cells from Somatic Tissue. https://doi.org/10.1101/2020.07.27.215103

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