Elucidation of Pathogenesis of Neutropenia Using iPS Cells and Genome Editing Technology

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07745
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: University of Tsukuba (2023); The University of Tokyo (2021-2022)
• Principal Investigator: Izawa Kiyoko 筑波大学, 附属病院, 研究員 (20534415)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 疾患特異的iPS / 好中球減少症 / 好中球分化

Outline of Final Research Achievements

Neutrophils play a crucial role in the initial defense against pathogens such as bacteria and fungi as immune cells. Therefore, neutropenia increases the risk of severe infections. This study aimed to elucidate the mechanisms of neutropenia caused by extremely rare gene mutations whose association with disease onset remains unclear, despite their identification. First, we successfully induced abnormal hematopoietic progenitor cells that closely resemble those in the disease from disease-specific iPS cells. Using these artificially created disease-specific cells for gene expression analysis, we revealed for the first time that one mechanism of neutropenia involves the suppression of various differentiation-related genes during the differentiation process.

Free Research Field

Hematopoietic Stem Cells

Academic Significance and Societal Importance of the Research Achievements

本研究では、これまで再現することができなかった希少疾患を疾患特異的iPS細胞を利用することで、初めて病態の再現に成功した。また、好好中球減少症発症メカニズムの一端を遺伝子発現レベルで初めて明らかにした。本研究結果は、希少な原因遺伝子を持つ好中球減少症のさらに詳細な発症メカニズムを解明する手がかりとなり、今後の治療法開発に向けた重要な知見になると考える。