Molecular mechanisms of region-specific cellular differentiation in the gastrointestinal epithelium.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08452
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: MORI Kentaro 金沢医科大学, 医学部, 助教 (50397296)
• Co-Investigator(Kenkyū-buntansha): 黒岡 尚徳 相模女子大学, 栄養科学部, 教授 (00293879) ; 中村 ハルミ 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 研究所 ゲノム病理ユニット ユニット長 (80164325)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 細胞分化 / 消化管上皮 / 遺伝子発現 / 転写因子 / がん

Outline of Final Research Achievements

The gastrointestinal epithelium is formed when tubular endoderm establishes region-specific cellular identity along its anterior-posterior axis. Many of the transcription factors which expressed in a region-specific manner and regulate endoderm differentiation also play important roles in maintaining adult epithelial homeostasis. Their dysregulation is closely related to the formation of ectopic epithelia and the development of cancer. However, it remains unclear how the region-specific expression of such transcription factors is regulated in the cell fate specification.We have previously found that Id2, a negative transcriptional factor, regulates the differentiation of the small intestinal epithelium through the suppression of foregut transcription factors Irx3/5.
In this study, we elucidate the mechanism of gastrointestinal epithelial cell fate determination based on inhibition of cell differentiation and to understand the mechanism of ectopic epithelial formation and tumorigenesis.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、正常組織構築に関わる分子機構の理解のみならず、細胞の脱制御による上皮異形成の発症機序を明らかにする上で有益な知見をもたらし、食道がんや胃がんに対する治療法の開発に貢献することが期待される。また、発生過程の分化調節メカニズムが明らかになることにより、多能性幹細胞から安全性の高い機能性消化管上皮細胞の作製といった再生医療の実現にも貢献できると思われる。