The Essential Functions of Adipo-osteogenic Progenitors as the Hematopoietic Stem and Progenitor Cell Niche
The Essential Functions of Adipo-osteogenic Progenitors as the Hematopoietic Stem and Progenitor Cell Niche
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DOI：
10.1016/j.immuni.2010.08.017
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发表时间：
2010-09-24
期刊：
影响因子：
32.4
通讯作者：
Nagasawa, Takashi
中科院分区：
文献类型：
--
作者：
Omatsu, Yoshiki;Sugiyama, Tatsuki;Nagasawa, Takashi
造血干细胞（hsc）及其淋巴造血后代由骨髓内的微环境生态位支持；然而，这些生态位的身份、性质和功能仍不清楚。短期消融体内富含CXC趋化因子配体（CXCL）12的网状（CAR）细胞不会影响候选壁龛、骨衬成骨细胞或内皮细胞，但会严重损害骨髓细胞的成脂和成骨分化潜能以及细胞因子SCF和CXCL12的产生，并导致循环淋巴和红系祖细胞显著减少。来自CAR细胞缺失小鼠的造血干细胞数量和细胞大小减少，更安静，并且早期骨髓选择基因的表达增加，与没有生态位培养的野生型造血干细胞的表型相似。因此，由脂肪成骨祖细胞组成的生态位对于造血干细胞、淋巴祖细胞和红祖细胞的增殖以及维持造血干细胞处于未分化状态是必需的。
Hematopoietic stem cells (HSCs) and their lympho-hematopoietic progeny are supported by microenvironmental niches within bone marrow; however, the identity, nature, and function of these niches remain unclear. Short-term ablation of CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells in vivo did not affect the candidate niches, bone-lining osteoblasts, or endothelial cells but severely impaired the adipogenic and osteogenic differentiation potential of marrow cells and production of the cytokines SCF and CXCL12 and led to a marked reduction in cycling lymphoid and erythroid progenitors. HSCs from CAR cell-depleted mice were reduced in number and cell size, were more quiescent, and had increased expression of early myeloid selector genes, similar to the phenotype of wild-type HSCs cultured without a niche. Thus, the niche composed of adipo-osteogenic progenitors is required for proliferation of HSCs and lymphoid and erythroid progenitors, as well as maintenance of HSCs in an undifferentiated state.