Regulation of erythroblast enucleation to improve the efficiency of mature erythrocyte production from stem cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K12785
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Ehime University
• Principal Investigator: Mitsuda Noriaki 愛媛大学, 医学系研究科, 教授 (10314329)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Cyclin D3 / プロテアソーム / 赤血球分化 / 脱核

Outline of Final Research Achievements

The cell cycle regulator Cyclin D3 is known to form a complex with Cdk4 and exert its kinase activity. The applicant found that Cyclin D3 is degraded by proteasomes during enucleation of mouse erythroblasts, that the progress of enucleation is delayed by artificially delaying the degradation of Cyclin D3, and that the delay in enucleation is canceled by the addition of Cdk4 inhibitors. These results suggest that degradation of Cyclin D3 by proteasomes and reduction of the kinase activity of the Cyclin D3-Cdk4 complex are triggers that induce enucleation, and that control of these factors can improve the efficiency of erythroblast enucleation.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

慢性的な輸血用血液不足や献血における未知の感染症の問題から、献血に頼らない新たな輸血用血液の供給システムの確立が必要とされている。そのためには多分化能を有する細胞から赤血球を作製する試みがなされているが、脱核の効率が悪く実用化に至っていない。申請者はプロテアソームによるCyclin D3の分解が脱核を誘導するトリガーであり、これを制御することによって赤芽球の脱核効率を改善できる可能性を見出した。本研究結果から、多分化能を有する細胞から効率よく赤血球を作製する薬剤の開発が可能となれば、社会的意義は極めて大きい。