来自澳大利亚马特医学研究所的科学家发现内皮细胞选择素可以促进造血干细胞的增殖,调控造血干细胞休眠、自我更新和化学抗性,是血管生境的重要组分。

-2012年11月《自然-医学》

中文翻译


【题目】血管生境中的内皮细胞选择素调控造血干细胞的休眠、自我更新和药物耐性

【译文】干细胞周围微环境或生境大大控制其细胞命运。造血干细胞(HSCs)两种解剖学生境已经在骨髓中被报道,但对于这些生境的不同功能还不清楚。本研究报道了血管HSC生境中完全由骨髓内皮细胞表达的粘附分子内皮细胞选择素的新作用。HSC休眠被增强了,其自我更新潜能在内皮细胞选择素敲除(Sele−/−)小鼠中或施予一种内皮细胞选择素拮抗剂后增加,这证实了内皮细胞选择素促进了HSC增殖,是血管生境的重要组分。这些效应不由典型内皮细胞选择素配体所介导。 化疗药物或辐射的小鼠治疗后,内皮细胞选择素的缺失或阻断会增强HSC的生存率达到3-6倍,并加速血液中性粒细胞恢复。因为骨髓抑制作用是高剂量化疗的严重副作用,内皮细胞选择素的瞬时阻断是化疗或放射期间HSCs保护的潜在治疗方法。

英文原稿


[Title]: Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance

[Authors]:Ingrid G Winkler,1 Valérie Barbier,1 Bianca Nowlan,2 Rebecca N Jacobsen,2, 3 Catherine E Forristal,2 John T Patton,4 John L Magnani4 & Jean-Pierre Lévesque2, 3

[Abstract]The microenvironment, or niche, surrounding a stem cell largely governs its cellular fate. Two anatomical niches for hematopoietic stem cells (HSCs) have been reported in the bone marrow, but a distinct function for each of these niches remains unclear. Here we report a new role for the adhesion molecule E-selectin expressed exclusively by bone marrow endothelial cells in the vascular HSC niche. HSC quiescence was enhanced and self-renewal potential was increased in E-selectin knockout (Sele−/−) mice or after administration of an E-selectin antagonist, demonstrating that E-selectin promotes HSC proliferation and is a crucial component of the vascular niche. These effects are not mediated by canonical E-selectin ligands. Deletion or blockade of E-selectin enhances HSC survival threefold to sixfold after treatment of mice with chemotherapeutic agents or irradiation and accelerates blood neutrophil recovery. As bone marrow suppression is a severe side effect of high-dose chemotherapy, transient blockade of E-selectin is potentially a promising treatment for the protection of HSCs during chemotherapy or irradiation.

原文地址

http://www.nature.com/nm/journal/v18/n11/abs/nm.2969.html

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