One-step induction of photoreceptor-like cells from human iPSCs by delivering transcription factors
Yuki Otsuka,
Keiko Imamura,
Akio Oishi,
Takayuki Kondo,
Mika Suga,
Yuichiro Yada,
Ran Shibukawa,
Yasue Okanishi,
Yukako Sagara,
Kayoko Tsukita,
Akitaka Tsujikawa,
Haruhisa Inoue
Affiliations
Yuki Otsuka
iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center, Kyoto, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
Keiko Imamura
iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center, Kyoto, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, Japan
Akio Oishi
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
Takayuki Kondo
iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center, Kyoto, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, Japan
Mika Suga
iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center, Kyoto, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
Yuichiro Yada
iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center, Kyoto, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
Ran Shibukawa
iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center, Kyoto, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
Yasue Okanishi
iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center, Kyoto, Japan
Yukako Sagara
iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center, Kyoto, Japan
Kayoko Tsukita
iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center, Kyoto, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
Akitaka Tsujikawa
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
Haruhisa Inoue
iPSC-based Drug Discovery and Development Team, RIKEN BioResource Research Center, Kyoto, Japan; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, Japan; Corresponding author
Summary: Retinal dystrophies (RDs) lead to irreversible vision impairment with no radical treatment. Although photoreceptor cells (PRCs) differentiated from human induced pluripotent stem cells (iPSCs) are essential for the study of RDs as a scalable source, current differentiation methods for PRCs require multiple steps. To address these issues, we developed a method to generate PRCs from human iPSCs by introducing the transcription factors, CRX and NEUROD1. This approach enabled us to generate induced photoreceptor-like cells (iPRCs) expressing PRC markers. Single-cell RNA sequencing revealed the transcriptome of iPRCs in which the genes associated with phototransduction were expressed. Generated iPRCs exhibited their functional properties in calcium imaging. Furthermore, light-induced damage on iPRCs was inhibited by an antioxidant compound. This simple approach would facilitate the availability of materials for PRC-related research and provide a useful application for disease modeling and drug discovery.
