Identification of genes specific to the intestinal epithelial stem cells and their functional analysis by making use of transgenic frogs

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K07475
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphology/Structure
• Research Institution: Nippon Medical School
• Principal Investigator: Hasebe Takashi 日本医科大学, 医学部, 准教授 (70329027)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 消化管 / 組織幹細胞 / 両生類 / 甲状腺ホルモン

Outline of Final Research Achievements

In the small intestine of Xenopus laevis during metamorphosis, which is caused by thyroid hormone (TH), most of the larval epithelial cells are removed by apoptosis whereas some of them dedifferentiate into the adult epithelial stem cells (SC), which actively proliferate and differentiate into the adult epithelial cells. To clarify the mechanisms of the stem cell regulation, identification and functional analysis of SC-specific genes were conducted.
We found by using the transgenic tadpoles expressing GFP specifically in the SCs that TH receptor (TR) alpha subtype is expressed in the SCs. In addition, we demonstrated that hyaluronan/CD44 signaling plays an important role for the stem cell regulation. Furthermore, we identified that winged-helix transcription factor Foxl1 is expressed in the connective tissue cells just beneath the SCs, suggesting the involvement of these cells in the stem cell niche formation.

Free Research Field

比較内分泌学、発生生物学

Academic Significance and Societal Importance of the Research Achievements

カエルの消化管をモデルとした本研究の成果により、組織幹細胞の制御機構（幹細胞がどのようにできるか、幹細胞がどのような仕組みで分化するかなど）の一端を明らかにすることができた。両生類独自の機構と脊椎動物共通の機構が存在すると考えられるが、いずれも幹細胞研究の発展には大きく貢献すると考えられる。また、哺乳類消化管の幹細胞制御機構と類似する点も多いことから、カエルを用いて得られた結果を再生医療などへ応用することも、将来的には可能になると考えている。