Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment

Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment
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DOI:
10.1016/j.cell.2007.08.025
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发表时间:
2007-10-19
期刊:
影响因子:
64.5
通讯作者:
Bianco, Paolo
Bianco, Paolo
中科院分区:
生物学1区
文献类型:
--
作者:
Sacchetti, Benedetto;Funari, Alessia;Bianco, Paolo

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在人骨髓(BM)中建立造血微环境(HME)的细胞和在BM基质中发现的克隆原性骨骼祖细胞的身份长期以来一直是难以捉摸的。我们表明,表达MCAM/CD 146的人骨髓基质中的内皮下细胞能够在移植后将HME转移到异位部位,这与在微型骨器官内建立相同的内皮下细胞一致。通过与发育中的血窦的特异性、动态相互作用,在体内发育中的异位BM中建立内皮下基质细胞。位于窦状隙壁上的内皮下基质细胞是血管生成素-1-(参与血管重塑的HSC "壁龛“的关键分子)的主要生产者。我们的数据揭示了体内HME的建立、骨髓窦状隙中骨骼祖细胞的建立和血管生成之间的功能关系。
The identity of cells that establish the hematopoietic microenvironment (HME) in human bone marrow ( BM), and of clonogenic skeletal progenitors found in BM stroma, has long remained elusive. We show that MCAM/CD146 expressing, subendothelial cells in human BM stroma are capable of transferring, upon transplantation, the HME to heterotopic sites, coincident with the establishment of identical subendothelial cells within a miniature bone organ. Establishment of subendothelial stromal cells in developing heterotopic BM in vivo occurs via specific, dynamic interactions with developing sinusoids. Subendothelial stromal cells residing on the sinusoidal wall are major producers of Angiopoietin-1-(a pivotal molecule of the HSC `` niche'' involved in vascular remodeling). Our data reveal the functional relationships between establishment of the HME in vivo, establishment of skeletal progenitors in BM sinusoids, and angiogenesis.