Nature:发现形成造血干细胞小生境的细胞身份

2010-08-13 00:00 · wythe

在骨髓中形成造血干细胞小生境的细胞身份一直不清楚。现在,Paul Frenette及其同事识别出,表达nestin的间叶干细胞为形成小生境的细胞。这些细胞与造血干细胞有密切物理关系,表达高水平的参与干细胞维护的基因,它们的删除会降低造血先祖细胞的骨髓寻的(homing)功能。 这

在骨髓中形成造血干细胞小生境的细胞身份一直不清楚。现在,Paul Frenette及其同事识别出,表达nestin的间叶干细胞为形成小生境的细胞。这些细胞与造血干细胞有密切物理关系,表达高水平的参与干细胞维护的基因,它们的删除会降低造血先祖细胞的骨髓寻的(homing)功能。

这项工作显示,骨髓中的干细胞小生境是两种截然不同的体干细胞(somatic stem-cell)类型之间的一种伙伴关系。

生物谷推荐原文出处:

Nature doi:10.1038/nature09262

Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

Simón Méndez-Ferrer,Tatyana V. Michurina,Francesca Ferraro,Amin R. Mazloom,Ben D. MacArthur,Sergio A. Lira,David T. Scadden,Avi Ma’ayan,Grigori N. Enikolopov" Paul S. Frenette

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.

关键词: