Study on the etiology of bipolar disorder using iPS cells

• Project/Area Number: 18K15507
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Chiba University
• Principal Investigator: ISHIMA Tamaki 千葉大学, 社会精神保健教育研究センター, 特任助教 (00597130)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 双極性障害 / iPS / 肝細胞

Outline of Final Research Achievements

Bipolar disorder (BD) is a popular psychiatric disorder; however, the precise pathology of BD is unknown. Recently we proposed the role of brain-liver axis in the pathology of psychiatric disorders such as BD. Human iPS cell technology is a useful tool to study the pathology of psychiatric disorders. In this study, we investigated the role of brain-liver axis in the pathology of BD using iPSC technology. First, we differentiated to hepatocyte cells from iPS cells from BD patients and healthy control subjects. To investigate the comprehensive screes, we performed RNA-seq analysis of these hepatocyte cells from two groups. Subsequently, we performed the DEG analysis and IPA analysis of the RNA-seq data. We found that some signal pathways may play a role in the pathology of BD. Detail experiments on some signaling pathways in BD pathology are underway.

Academic Significance and Societal Importance of the Research Achievements

双極性障害は統合失調症と並ぶ代表的な精神疾患であるが、その病因に関わる詳細な機序は不明である。また、古くから、双極性障害患者には肝障害を有する割合が高いことが知られているがその詳細は不明である。
多能性幹細胞(iPS細胞)は精神医学領域においても応用されているがこの領域における殆どの研究は神経に分化させた神経細胞を用いたものが主であり、肝臓などの末梢臓器細胞などに分化させたものを用いた研究は今までなかった。今回の研究では双極性障害患者由来のiPS細胞を肝細胞に分化させることにより、脳-肝連関の視点から双極性障害の病因解明の糸口となる遺伝子を見いだすことが出来た。