Identification of novel homing molecules of hematopoietic stem cells and development of efficient bone marrow transfer methods by modifying carbohydrates

我们发现β4GalT-I缺陷的骨髓(BM)细胞不能植入X射线辐射野生型小鼠的BM。不仅β4GalT-I基因缺陷的骨髓细胞不能建立受体小鼠的造血系统，而且在骨髓移植后不久，它们在骨髓中的植入明显减少，表明造血干细胞(HSC)在骨髓中的归巢受到了损害。接下来，我们调查了Gne基因发生点突变的小鼠，该基因编码唾液酸生物合成的关键酶。来自Gne点突变小鼠的骨髓细胞的归巢效率降低到野生型小鼠的一半，尽管这种减少并不像Beta4GalT-I缺陷小鼠那样明显。这些结果表明，糖链末端的唾液酸也在HSC归巢中发挥作用。

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.