Significance of glycan diversity of cKit-labeled niche cells in homeostasis of colon epithelium

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07275
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Kyorin University
• Principal Investigator: Sugahara Daisuke 杏林大学, 医学部, 助教 (00390766)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: ニッチ細胞 / ムチン / 糖鎖 / 腸管上皮 / 免疫組織化学染色 / レクチン

Outline of Final Research Achievements

Elucidation of the mechanism to maintain the homeostasis of the intestinal epithelium is an important issue that leads to the understanding of intestinal diseases. cKit+ cells at the base of colonic crypts are known as niche cells that regulate stem cells. However, their cellular property and particular role in the mechanism are largely unveiled. Here, our immunohistochemical analysis of the mouse colon clarified differences in stem cell regulation by cKit+ cells along the proximal-distal axis of the colon. We also showed that cKit+ cells are mucin-producing cells with different properties from goblet cells in the middle to upper crypt. They secreted mucins with a particular glycan, which are highly likely to contribute to the maintenance and regeneration of the epithelium. These results raised the novel possibility that a defect in cKit+ cells is deeply involved in intestinal diseases in terms of mucin production (especially regulating glycosylation) as well as stem cell regulation.

Free Research Field

解剖学

Academic Significance and Societal Importance of the Research Achievements

cKit陽性細胞の糖鎖発現への着目から、その組織学的特徴と、上皮の恒常性維持に寄与する多様な機能が明らかになった。幹細胞制御のみならず、ムチン産生においても特有の機能を有した。その細胞状態と役割は、近位-遠位軸に沿った大腸の部位や再生過程など腸管の状況に応じて調整されることも示した。大腸上皮の細胞構築を理解する上で新たな知見であると同時に、恒常性を維持する精緻な機構の一端を解明した。腸管内腔を覆うムチン層、特にその付加糖鎖の異常は腸疾患と関連が深い。cKit陽性細胞の不具合は、ムチン産生と幹細胞制御、両方の異常を介し腸疾患と関連する可能性が高く、病因・病態を理解する上で重要な細胞を見出した。