Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche.
Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche.
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DOI：
10.1038/nature16943
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发表时间：
2016-02-11
期刊：
影响因子：
64.8
通讯作者：
Weissman IL
中科院分区：
文献类型：
--
作者：
Chen JY;Miyanishi M;Wang SK;Yamazaki S;Sinha R;Kao KS;Seita J;Sahoo D;Nakauchi H;Weissman IL
造血干细胞（HSC）是最广泛表征的组织干细胞。由于其识别的前瞻性分离，复杂的多参数流式细胞仪分离的表型子集，促进了研究的许多方面的HSC生物学，包括自我更新，分化，老化，生态位和多样性。在这里，我们证明了无偏多步筛选，一个单一的基因，Hoxb 5（同源框B5也被称为Hox-2.1），其在骨髓（BM）中的表达是有限的长期HSC（LT-HSC）在小鼠的鉴定。利用由内源性Hoxb 5调节驱动的单色tri-mCherry报告小鼠，只有Hoxb 5阳性HSC在初次移植受体中移植后表现出长期重建能力，并且在二次移植受体中表现出长期重建能力。只有7-35%的各种先前定义的免疫表型HSC是LT-HSC。最后，通过小鼠BM的原位成像，我们显示>94%的LT-HSC（Hoxb 5+）直接附着于VE-钙粘蛋白阳性细胞，暗示血管周围空间作为LT-HSC的接近均匀的定位。
The hematopoietic stem cell (HSC) is arguably the most extensively characterized tissue stem cell. Since its identification by prospective isolation, complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology including, self-renewal, differentiation, aging, niche, and diversity. Here we demonstrate by unbiased multi-step screening, identification of a single gene, Hoxb5 (homeobox B5 also known as Hox-2.1), whose expression in the bone marrow (BM) is limited to the long-term HSC (LT-HSC) in mice. Utilizing a single-color tri-mCherry reporter mouse driven by endogenous Hoxb5 regulation, only the Hoxb5-positive HSCs exhibit long-term reconstitution capacity after transplantation in primary transplant recipients, and critically, in secondary recipients. Only 7–35% of various previously defined immunophenotypic HSCs are LT-HSCs. Finally, by in situ imaging of mouse BM, we show that >94% of LT-HSC (Hoxb5+) are directly attached to VE-cadherin-positive cells, implicating a perivascular space as a near homogenous localization of the LT-HSC.