Glycosilation of glycosaminoglycan in bone marrow affect in hematopoiesis and GVHD after BM transplantation

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09868
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Niigata University
• Principal Investigator: MASUKO MASAYOSHI 新潟大学, 医歯学総合病院, 准教授 (70397115)
• Co-Investigator(Kenkyū-buntansha): 五十嵐 道弘 新潟大学, 医歯学系, 教授 (50193173) ; 牛木 隆志 新潟大学, 医歯学総合病院, 講師 (80579152)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: コンドロイチン硫酸 / 造血幹細胞 / 造血ニッチ

Outline of Final Research Achievements

Chondroitin sulfate (CS), a glycosaminoglycan, is a major component of the extracellular matrix; however, it is not known whether CS has a physiological role in the hematopoiesis in BM. We analyzed the effects of CS on the BM microenvironment using knockout of N-acetylgalactosaminyltransferase-1, a key enzyme for CS biosynthesis that is important for regulating CS levels. HSPCs from T1KO mice showed significantly impaired repopulation in WT recipient mice upon serial transplantation. In contrast, the number of WT HSPCs repopulated in T1KO recipient mice was greater than that in WT recipient mice after serial transplantation, indicating that the T1KO BM niche supports repopulation of HSPCs better than the WT BM niche. RNA sequence analysis revealed that HSPCs in T1KO is associated with activation of the IFN-α/β signal and endoplasmic reticulum stress.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究によりコンドロイチン硫酸は造血ニッチ、造血幹細胞それぞれで造血分化に異なる作用を示すことが明らかになった。造血細胞移植時の前処置、老化によりコンドロイチン硫酸量は変化しすると考えられ、本研究の結果は糖鎖修飾による造血細胞移植後の生着促進や老化に伴う造血不全症、白血病の新しい視点からの治療法の開発につながる。