Identification and functional analysis of colonic label-retaining goblet cells for the application to regeneration of the inflamed mucosa.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03634
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Okamoto Ryuichi 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50451935)
• Co-Investigator(Kenkyū-buntansha): 油井 史郎 東京医科歯科大学, 統合研究機構, 准教授 (00383886)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 杯細胞 / 炎症性腸疾患 / 粘膜再生

Outline of Final Research Achievements

We successfully identified 37 highly expressed genes in the mice's proximal colon secretory cells (goblet cells). Also, 70 genes were identified as highly expressed genes in the mice's distal colon secretory cells (goblet cells), including Reg family genes. GSEA analysis of the gene expression profile indicated high expression of the quiescent stage genes in candidate label-retaining goblet cells. We also performed a microarray analysis of human organoids derived from the ascending colon or the rectum. From those data, we identified 43 genes preferentially expressed in the rectum-derived organoids and 47 expressed in the ascending colon-derived organoids.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

マウス近位大腸杯細胞を単離・同定するための複数の分子マーカー及び候補遺伝子群及びヒト近位大腸上皮に一定の発現特異性を有する遺伝子群の同定に成功しており、大腸近位に存在する杯細胞が如何なる特性・機能を有し制御・誘導され、大腸粘膜の恒常性に貢献しているのかを解明するための基盤となる知見が獲得された。また、同杯細胞に特異的な機能等を活用し異なる大腸区域に由来する「自家腸上皮オルガノイド」を移植治療に利用しながら、「大腸粘膜の区域特性変換」による炎症粘膜再生治療を開発するための基盤となる知見も併せて獲得された。