Mesenchymal and haematopoietic stem cells form a unique bone marrow niche.
Mesenchymal and haematopoietic stem cells form a unique bone marrow niche.
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作者：
骨髓中形成造血干细胞(HSC)生态位的细胞成分尚不清楚，研究涉及成骨细胞、内皮细胞和血管周围细胞。在这里，我们证明了间充质干细胞(MSCs)，通过巢蛋白的表达鉴定，构成了HSC的一个重要的生态位成分。Nestin+MSCs具有所有的骨髓集落形成单位成纤维细胞活性，可以作为非贴壁的“中间球”在连续移植中自我更新和扩张。Nestin+MSCs在空间上与HSC和肾上腺素能神经纤维相关，并高度表达HSC维持基因。这些基因和其他触发成骨细胞分化的基因，在强制动员造血干细胞或激活β3肾上腺素受体的过程中，被选择性地下调。甲状旁腺激素可使骨髓中Nestin+细胞的数量增加一倍，并有利于其成骨分化，而体内Nestin+细胞的耗尽会迅速降低骨髓中HSC的含量。纯化的HSCs在致死照射小鼠的骨髓中接近Nestin+MSCs，而在体内Nestin+细胞的枯竭显著减少造血祖细胞的骨髓归巢。这些结果揭示了两种不同的体细胞类型之间史无前例的合作关系，并表明了由异型干细胞对组成的骨髓中一种独特的利基。
The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin+ MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent ‘mesenspheres’ that can self-renew and expand in serial transplantations. Nestin+ MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or β3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin+ cells and favours their osteoblastic differentiation, in vivo nestin+ cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin+ MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin+ cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.
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影响因子：
3
作者：
Berger SI;Posner JM;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
DOI：
10.1196/annals.1402.086
发表时间：
2007-01-01
期刊：
SKELETAL BIOLOGY AND MEDICINE, PT A
影响因子：
--
作者：
Mendez-Ferrer, Simon;Frenette, Paul S.
通讯作者：
Frenette, Paul S.
影响因子：
64.5
作者：
Sacchetti, Benedetto;Funari, Alessia;Bianco, Paolo
通讯作者：
Bianco, Paolo
影响因子：
48
作者：
Buch, T;Heppner, FL;Waisman, A
通讯作者：
Waisman, A