One-step induction of photoreceptor-like cells from human iPSCs by delivering transcription factors

通过递送转录因子一步诱导人类 iPSC 产生感光样细胞

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作者:Yuki Otsuka, Keiko Imamura, Akio Oishi, Takayuki Kondo, Mika Suga, Yuichiro Yada, Ran Shibukawa, Yasue Okanishi, Yukako Sagara, Kayoko Tsukita, Akitaka Tsujikawa, Haruhisa Inoue

Abstract

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.

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