Epithelial cell plasticity and reversibility of primitive endodermal tissues

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03657
• 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: Yui Shiro 東京医科歯科大学, 統合研究機構, 准教授 (00383886)
• Co-Investigator(Kenkyū-buntansha): 武部 貴則 東京医科歯科大学, 統合研究機構, 教授 (20612625) ; 柿沼 晴 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30372444)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 細胞外基質依存性上皮細胞可塑性

Outline of Final Research Achievements

I formally presented the scheme that the interaction of Type I Collagen and epithelial cells induce the reprogramming of cellular character from adult mature phenotype towards fetal primitive one by using murine intestine as a model. This fetal induction is now recognized as one of the important regenerative responses of intestinal epithelial cells to drive a quick restoration of tissue homeostasis. The spherical intestinal organoids organized in purified Type I Collagen is already revealed to be an enriched population of these reprogrammed epithelial cells, the mechanisms are not well defined yet. This study clearly identified not only the key transcriptional factors governing the process, but also the similar regenerative reaction in human samples. Furthermore, this study illustrates how to adapt the mechanisms to artificially induce the compatible signature between intestine and liver, both of which developed from the same primitive gut tube.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、炎症性腸疾患などの難治性腸疾患における上皮細胞に特有の炎症特性をすべからく理解するための演繹手法として非常に有用です。すなわち、本研究課題で提示した分子的スキームを当てはめることにより、従来の網羅的発現遺伝子解析やゲノムワイド解析などの結果を体系的に理解し、細部に渡るまで論理的に理解することができるようになりました。これは腸研究における極めて重大な研究成果です。さらに本課題では、その機序を人為的に利用して、細胞特性を遺伝子操作によらない手法で互換させるという全く新しい細胞工学的手法を提唱した点で社会的インパクトがあります。