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Inducing Human Retinal Pigment Epithelium-like Cells from Somatic Tissue

Ivo Ngundu Woogeng, Imad Abugessaisa, Akihiro Tachibana, Yoshiki Sahara, Chung-Chau Hon, Akira Hasegawa, Bogumil Kaczkowski, Noriko Sakai, Mitsuhiro Nishida, Haiming Hu, Hashimita Sanyal, Junki Sho, Takeya Kasukawa, Minoru Takasato, Piero Carninci, Akiko Maeda, Michiko Mandai, Erik Arner, Masayo Takahashi, Cody Kime
doi: https://doi.org/10.1101/2020.07.27.215103
Ivo Ngundu Woogeng
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
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Imad Abugessaisa
2RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
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Akihiro Tachibana
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
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Yoshiki Sahara
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
3Laboratory of Molecular Cell Biology and Development, Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan
4Department of Renal and Cardiovascular Research, New Drug Research Division, Otsuka Pharmaceutical Co. Ltd., Tokushima 771-0192, Japan
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Chung-Chau Hon
2RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
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Akira Hasegawa
2RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
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Bogumil Kaczkowski
2RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
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Noriko Sakai
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
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Mitsuhiro Nishida
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
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Haiming Hu
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
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Hashimita Sanyal
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
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Junki Sho
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
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Takeya Kasukawa
2RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
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Minoru Takasato
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
3Laboratory of Molecular Cell Biology and Development, Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan
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Piero Carninci
2RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
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Akiko Maeda
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
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Michiko Mandai
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
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Erik Arner
2RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan
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Masayo Takahashi
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
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Cody Kime
1RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
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  • For correspondence: cody.kime@riken.jp
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SUMMARY

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.

Competing Interest Statement

CONFLICTS OF INTEREST C.K., M.T., and I.N.W have filed for patent on related technology.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted July 27, 2020.
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Inducing Human Retinal Pigment Epithelium-like Cells from Somatic Tissue
Ivo Ngundu Woogeng, Imad Abugessaisa, Akihiro Tachibana, Yoshiki Sahara, Chung-Chau Hon, Akira Hasegawa, Bogumil Kaczkowski, Noriko Sakai, Mitsuhiro Nishida, Haiming Hu, Hashimita Sanyal, Junki Sho, Takeya Kasukawa, Minoru Takasato, Piero Carninci, Akiko Maeda, Michiko Mandai, Erik Arner, Masayo Takahashi, Cody Kime
bioRxiv 2020.07.27.215103; doi: https://doi.org/10.1101/2020.07.27.215103
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Inducing Human Retinal Pigment Epithelium-like Cells from Somatic Tissue
Ivo Ngundu Woogeng, Imad Abugessaisa, Akihiro Tachibana, Yoshiki Sahara, Chung-Chau Hon, Akira Hasegawa, Bogumil Kaczkowski, Noriko Sakai, Mitsuhiro Nishida, Haiming Hu, Hashimita Sanyal, Junki Sho, Takeya Kasukawa, Minoru Takasato, Piero Carninci, Akiko Maeda, Michiko Mandai, Erik Arner, Masayo Takahashi, Cody Kime
bioRxiv 2020.07.27.215103; doi: https://doi.org/10.1101/2020.07.27.215103

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