Analysis of galactose carbohydrates regulating homing and differentiation of HSC in the bone marrow niche

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02389
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Kyoto University
• Principal Investigator: ASANO Masahide 京都大学, 医学研究科, 教授 (50251450)
• Co-Investigator(Kenkyū-buntansha): 成瀬 智恵 京都大学, 医学研究科, 准教授 (30372486)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨髄移植 / 造血幹細胞 / ホーミング / ゲノム編集

Outline of Final Research Achievements

From studies on the glycan function of CXCR4, which is important for homing of hematopoietic stem cells (HSCs) to the bone marrow after transplantation, we found that two O-glycosylation sites located at the N-terminus of CXCR4 are important. Mutant CXCR4 without O-glycosylation at these sites failed to promote migration activity of cultured cells. Transplantation of CXCR4-deficient fetal liver-derived HSCs transfected with the mutant CXCR4 did not enhance homing of HSCs, unlike the wild type, and transplantation of bone marrow-derived HSCs from genome-edited CXCR4 mutant mice reduced homing activity to less than half that of the control HSCs. These results indicate that the O-glycosylation site of CXCR4 is required for homing of HSCs.

Free Research Field

実験動物学

Academic Significance and Societal Importance of the Research Achievements

本研究によりHSCの移植後の骨髄へのホーミングにCXCR4の糖鎖が重要な役割を担っていることがわかった。造血幹細胞移植，特に臍帯血移植において生着不全の原因の一つに糖鎖不全が関わる可能性が考えられる。まずはCXCR4分子などの糖鎖不全をスクリーニングすることで生着不全のHSCを排除することができるかもしれない。また，HSCの糖鎖不全をin vitroで酵素的に修復することも今後研究が進むことが期待される。より安全で効率的なHSC移植医療の発展への貢献が期待される。