Myeloproliferation and hematopoietic stem cell dysfunction due to defective Notch receptor modification by O-fucose glycans.
Myeloproliferation and hematopoietic stem cell dysfunction due to defective Notch receptor modification by O-fucose glycans.
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由于 O-岩藻糖聚糖对 Notch 受体修饰有缺陷，导致骨髓增殖和造血干细胞功能障碍。
DOI：
10.1007/s00281-012-0303-2
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发表时间：
2012
影响因子：
9
通讯作者：
Zhou,Lan
中科院分区：
文献类型：
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作者：
Zhou,Lan
Notch细胞外结构域表皮生长因子（EGF）重复序列上的0-岩藻糖基聚糖通过改变Notch受体对Notch配体激活的敏感性来调节Notch信号传导。缺乏NotchO-岩藻糖基聚糖的小鼠表现出粒-单核细胞骨髓增殖、造血干细胞功能障碍和异常干细胞生态位占据。缺乏NotchO-岩藻糖基聚糖的干细胞/祖细胞不能转录Notch信号传导激活归因于有效Notch-配体相互作用的丧失。这些发现与在具有缺陷性Notch切割或配体内吞作用的小鼠模型中鉴定的骨髓增殖结合，揭示了Notch在造血干细胞生物学和骨髓稳态中的新作用。
O-fucosylglycans on Notch extracellular domain epidermal growth factor (EGF) repeats are critical in modulating Notch signaling by altering the sensitivity of Notch receptors to activation by Notch ligands. Mice lacking NotchO-fucosylglycans display granulo-monocytic myeloproliferation, hematopoietic stem cell dysfunction and aberrant stem cell niche occupancy. The inability of the stem cells/progenitors that lack NotchO-fucosylglycans to transcribe Notch signaling activation is attributed by a loss of effective Notch–ligand interaction. These findings, in conjunction with myeloproliferation identified in mouse models with defective Notch cleavage or ligand endocytosis, reveal emerging new roles of Notch in hematopoietic stem cell biology and myeloid homeostasis.