Roles of a non-coding RNA that regulates normal and neoplastic T cell development

2021 Fiscal Year Final Research Report

• Project/Area Number: 19KK0222
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: Tokyo University of Science
• Principal Investigator: Ikawa Tomokatsu 東京理科大学, 研究推進機構生命医科学研究所, 教授 (60450392)
• Co-Investigator(Kenkyū-buntansha): 高野 淳一朗 国立研究開発法人理化学研究所, 生命医科学研究センター, 特別研究員 (00852162) ; 磯田 健志 東京医科歯科大学, 医学部附属病院, 助教 (80815225)
• Project Period (FY): 2019-10-07 – 2022-03-31
• Keywords: 非コードRNA / T細胞分化 / 胸腺 / エピジェネティクス / 転写因子

Outline of Final Research Achievements

Non-coding RNA is involved in various life phenomena, whereas the molecular mechanism is largely unknown. We focused on the role of ThymoD, which is a non-coding RNA exclusively expressed in the thymus. We generated the induced Leukocyte Stem (iLS) cells from bone marrow of ThymoD-deficient mice. The ThymoD-deficient iLS cells fail to differentiate into T cells and express Bcl11b, suggesting that the ThymoD is critical for the expression of Bcl11b and further T cell differentiation. On the other hand, we identified the human ThymoD-BCL11B locus in normal and malignant T cells for the first time in the world. The blockade of the transcription of human ThymoD affected the epigentic modification of BLC11B loci, suggesting that the ThymoD is essential for both mouse and human T cell development.

Free Research Field

免疫学、血液学

Academic Significance and Societal Importance of the Research Achievements

我々は機能が不明なノンコーティングRNA（ThymoD）に着目し、ThymoDのT細胞分化における役割を解析した。その結果、ThymoDがT細胞の分化や腫瘍化に重要であることが明らかとなった。また、ThymoDはヒト正常T細胞やT細胞性白血病細胞にも発現し機能的であることを世界で初めて発見した。これにより、ThymoDを標的とした白血病の新規治療法の開発に結びつくことが期待される。