Study on photoreceptor cell differentiation using cloned photoreceptor cell precursor

Research Project

Project/Area Number	16K11334
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Ophthalmology
Research Institution	St. Marianna University School of Medicine
Principal Investigator	Suzuki Noboru 聖マリアンナ医科大学, 医学部, 教授 (40235982)
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2018: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000) Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000) Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords	網膜視細胞 / 杆体細胞 / 錐体細胞 / SDF1 / 視細胞分化 / 甲状腺ホルモン合成経路 / 再生医学 / 移植・再生医療 / 網膜 / 視細胞
Outline of Final Research Achievements	Among the retinal neural progenitor cells, the pax6-transfected iPS cells established by us correspond to photoreceptor precursors in mice. However, the differentiation mechanism of the photoreceptors is not so clear. We conducted an total transcriptome analysis of the cloned photoreceptor precursor upon SDF1 stimulation using next generation sequencer. We found that activation of the thyroid hormone synthesis pathway [KEGG:04918], nitrogen metabolism pathway [KEGG:00910], and prostate cancer pathway [KEGG:05215] is taking place in this cell by SDF1 stimulation that induces differentiation into rod photoreceptors. It has already been known that the expression of thyroid hormone receptor beta occurs upon differentiation into rod photoreceptors. Our findings confirmed involvement of thyroid hormone pathway for the rod photoreceptor differentiation and extended in more detail of the differentiation.
Academic Significance and Societal Importance of the Research Achievements	視細胞前駆細胞から視細胞への分化メカニズムや細胞相互の関連性はあまり明らかではない。我々が樹立した株化 pax6導入iPS細胞は網膜神経前駆細胞の中でも視細胞前駆細胞に相当する分化段階の細胞である。この細胞を用いて視細胞前駆細胞の分化機構を解析した。そこでこの細胞をSDF1刺激して経時的に網羅的トランスクリプトーム解析を行った。これまでに視細胞に対して網羅的トランスクリプトーム解析は行われておらず、極めて独創性の高い研究である。臨床的には全く分子病態の明らかではない色覚異常をもたらす分子を同定できる可能性がある。同時に現時点では知られていない視細胞の全く新規な病態を明らかにする可能性も高い。