Role of Notch signaling in early T cell development

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16331
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Tokai University
• Principal Investigator: Hirano Ken-ichi 東海大学, 医学部, 特定研究員 (70535228)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: T細胞 / Notchシグナル / 初期T細胞分化 / 造血前駆細胞

Outline of Final Research Achievements

We established lymphoid progenitor cell lines lacking Notch1 and/or Notch2 derived from Cas9-expressing Ebf1-deficient mice. We found that Tcf7, one of the earliest and functional Notch targets, is not fully activated by Notch2. Moreover, T cell differentiation was partially restored by the overexpression of Tcf7 with Notch2 signaling in Notch1-deficient cells.　These results suggest that Notch signaling induces early T cell differentiation via Tcf7-dependent and Tcf7-independent pathways.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、これまで困難であったT細胞の初期発生を誘導するNotchシグナルの標的遺伝子の網羅的な解析を行った。NotchシグナルはT細胞の発生だけでなくT細胞急性リンパ性白血病の発症にも深く関与しており、本研究による成果は、Notchシグナルによる分子制御機構を理解する上で重要な知見であると考えている。