Analysis of the mechanism of chronic kidney disease by forward genetics on kidney organoids

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17699
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: SUSA Koichiro 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (50735842)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 腎臓オルガノイド / 修飾遺伝子(modifier gene) / forward genetics / 慢性腎臓病(CKD) / 常染色体優性多発性嚢胞腎

Outline of Final Research Achievements

CKD is a national disease in Japan, however, the drastic treatment of CKD has not been established due to lack of systematic elucidation of CKD mechanism. We have hypothesized that some unidentified modifier genes play a role to aggravates fibrosis on CKD. Our purpose is identification of those modifier genes using kidney organoids, which are differentiated from induced pluripotent stem cells (iPSCs). In this study, we notice NPHP1, which is a causative gene which induces fibrosis in stromal tissues of the kidney. Initially we generated mutant iPSCs with genetically fibrotic phenotype to utilize for screening of modifier genes. In addition, we prepared reporters to visualize fibrotic lesions.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

腎臓線維化の増悪因子を見つけるのに利用するため、線維化を起こす遺伝性腎疾患と同じ変異を持つiPS細胞を作製した。また、線維化レポーターも作製し、線維化した領域を蛍光発色して可視化できるような仕組みをiPS細胞の内部に組み込んだ。これらの成果物を腎臓オルガノイドと組み合わせることにより、今後腎臓オルガノイド上での腎線維化の可視化をする実験の実現可能性を示したことになる。さらに、腎臓線維化を増悪させる修飾遺伝子を同定し、最終的には慢性腎臓病の治療法開発につなげたい。