Fate determination and function acquisition during induction/regeneration of photoreceptors from human somatic cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670741
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: National Rehabilitation Center for Persons with Disabilities
• Principal Investigator: SEKO YUKO 国立障害者リハビリテーションセンター(研究所), 研究所 感覚機能系障害研究部, 室長 (60301157)
• Co-Investigator(Kenkyū-buntansha): AZUMA Noriyuki 独立行政法人国立成育医療研究センター, 病院眼科・研究所 視覚科学研究室, 室長 (10159395) ; UMEZAWA Akihiro 独立行政法人国立成育医療研究センター, 再生医療センター, センター長 (70213486)
• Co-Investigator(Renkei-kenkyūsha): KANEDA Makoto 日本医科大学, 医学系研究科 システム生理学, 教授 (30214480)
• Research Collaborator: Komuta Yukari
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 眼発生 / 再生医学 / 網膜視細胞 / 直接的分化誘導

Outline of Final Research Achievements

Direct reprogramming is a promising, simple, low-cost approach to generate target cells from somatic cells without using induced pluripotent stem cells.　We generated photosensitive photoreceptor-like cells from human iris cells, human dermal fibroblasts and peripheral blood mononuclear cells (PBMCs) by transduction of photoreceptor-related transcription factors (CRX & RAX & OTX2 & NeuroD) via retrovirus vectors and Sendai virus vectors. We found that retinal disease-related genes were efficiently detected in CRX-transduced PBMCs. To improve differentiation levels, we made differentiation conditions close to the in vivo retinal development, such as the expression order of transcription factors and cooperation with retinal pigment epithelium. These modifications facilitated the differentiation of human PBMCs into photoreceptor-like cells. Our induced photoreceptor-like cells might contribute to individualized drug screening and disease modeling of inherited retinal degeneration.

Free Research Field

網膜分化、眼科学