Identification of novel homing molecules of hematopoietic stem cells and development of efficient bone marrow transfer methods by modifying carbohydrates
β4GalT-I欠損マウスの骨髄細胞はX線照射した野生型マウスに移植しても，レシピエントの骨髄に生着しないことを見いだした。β4GalT-I欠損骨髄細胞はレシピエントの造血系を再構築できないだけでなく，移植後短時間での骨髄への生着が顕著に減少しており，骨髄幹細胞（HSC）の骨髄へのホーミングが障害されていた。次に，シアル酸合成の鍵酵素であるGNE遺伝子の点変異マウス（シアル酸の合成が低下）の骨髄細胞を用いて移植を行ったところ，β4GalT-I欠損骨髄細胞ほどではないが，骨髄へのホーミングが半分程度に減少し，シアル酸もHSCの骨髄へのホーミングに重要であることが示唆された。
We have found that beta4GalT-I-deficient bone marrow (BM) cells cannot engraft in the BM of X-ray radiated wild-type mice. Not only beta4GalT-I-deficient BM cells cannot establish hematopoietic system of recipient mice, but also their engraftment into the BM shortly after BM transfer was markedly reduced, indicating that homing of hematopoietic stem cells (HSC) into the BM was impaired. We next investigated mice having a point mutation in the GNE gene, that encodes a key enzyme for sialic acids biosynthesis. Homing efficiency of BM cells from GNE point-mutant mice was reduced to half that of wild-type mice, although the reduction was not prominent as in beta4GalT-I-deficient mice. These results suggest that sialic acids at the terminus of carbohydrate chains also play a role in HSC homing.
骨髄幹細胞の新規ホーミング分子の同定と糖鎖修飾による効率的骨髄移植法の開発
.png)
FR-PR-ASANO-M-kaken 2014-4p.pdf
(186.68KB)
