Regulation of intestinal stem cells in inflammatory bowel disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15759
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Nagoya City University
• Principal Investigator: Katano Takahito 名古屋市立大学, 医薬学総合研究院(医学), 助教 (50768372)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 幹細胞 / KLF

Outline of Final Research Achievements

Kruppel-like factor 4 (KLF4) is a zinc-finger transcription factor, expressed in villus cells of the intestinal epithelium, that promotes cellular differentiation and tissue homeostasis. The aim of this study was to investigate how KLF4 contributes to crypt regeneration originated from BMI1＋ intestinal stem cell (ISC) lineage during homeostasis. KLF4 is positively correlated with goblet cell differentiation in BMI+ ISC derived lineage. Irradiate to single sorted BMI1-YFP+ cell derived organoid model reconstitute in vivo response following γ-irradiation . These results suggest that KLF4 regulates goblet cell differentiation during homeostasis and plays a radio-protective role.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

本研究では、転写因子KLF4が消化管幹細胞機能を制御し、組織恒常性維持・粘膜傷害時の再生に関与していることを明らかにした。KLF4はとくに組織恒常性維持においては杯細胞分化を制御していることが示唆され、炎症時の消化管バリア機能の制御においても重要な役割を持つことが示唆される。また、オルガノイドを用いて、放射線照射後の粘膜傷害後の生体内の再生の過程を、ex-vivoで再現することを可能とし、これは正常時のみならず粘膜傷害時の小腸上皮の幹細胞機能制御機構の解明のために有用な研究モデルとなる。