Isolation and characterization of endosteal niche cell populations that regulate hematopoietic stem cells
Isolation and characterization of endosteal niche cell populations that regulate hematopoietic stem cells
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DOI：
10.1182/blood-2009-08-239194
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发表时间：
2010-09-02
期刊：
影响因子：
20.3
通讯作者：
Suda, Toshio
中科院分区：
文献类型：
--
作者：
Nakamura, Yuka;Arai, Fumio;Suda, Toshio
骨内膜小生境对于造血干细胞（HSC）的维持至关重要。然而，它是由一个异质群体的分化阶段和功能。在这项研究中，我们的特点是骨内膜细胞群，并检查他们的能力，以维持造血干细胞。骨髓内骨内膜细胞分为未成熟间充质细胞富集的ALCAM（-）Sca-1（+）细胞、成骨细胞富集的ALCAM（+）Sca-1（-）细胞和ALCAM（-）Sca-1（-）细胞。我们发现，所有3个馏分保持长期重建（LTR）的活性，在体外培养的HSC。特别是，ALCAM（+）Sca-1（-）细胞通过上调HSC中归巢和细胞粘附相关基因显著增强HSC的LTR活性。微阵列分析显示，ALCAM（-）Sca-1（+）组分高表达丝氨酸相关基因，而ALCAM（+）Sca-1（-）组分表达多种细胞粘附分子，如钙粘蛋白，其表达水平高于其他组分，表明HSC与成骨细胞通过细胞粘附分子的相互作用增强了HSC的LTR活性。此外，我们在ALCAM（+）Sca-1（-）组分中发现了成骨细胞标记物（低/-）亚群，其表达细胞因子，如Angpt 1和Thpo，以及干细胞标记物基因。总之，这些数据表明，成骨细胞和间充质祖细胞的多个子集构成了骨内膜龛，并调节成体骨髓中的HSC。（血。2010;116（9）：1422-1432）
The endosteal niche is critical for the maintenance of hematopoietic stem cells (HSCs). However, it consists of a heterogeneous population in terms of differentiation stage and function. In this study, we characterized endosteal cell populations and examined their ability to maintain HSCs. Bone marrow endosteal cells were subdivided into immature mesenchymal cell-enriched ALCAM(-)Sca-1(+) cells, osteoblast-enriched ALCAM(+)Sca-1(-), and ALCAM(-)Sca-1(-) cells. We found that all 3 fractions maintained long-term reconstitution (LTR) activity of HSCs in an in vitro culture. In particular, ALCAM(+)Sca-1(-) cells significantly enhanced the LTR activity of HSCs by the up-regulation of homing- and cell adhesion-related genes in HSCs. Microarray analysis showed that ALCAM(-)Sca-1(+) fraction highly expressed cytokine-related genes, whereas the ALCAM(+)Sca-1(-) fraction expressed multiple cell adhesion molecules, such as cadherins, at a greater level than the other fractions, indicating that the interaction between HSCs and osteoblasts via cell adhesion molecules enhanced the LTR activity of HSCs. Furthermore, we found an osteoblastic marker(low/-) subpopulation in ALCAM(+)Sca-1(-) fraction that expressed cytokines, such as Angpt1 and Thpo, and stem cell marker genes. Altogether, these data suggest that multiple subsets of osteoblasts and mesenchymal progenitor cells constitute the endosteal niche and regulate HSCs in adult bone marrow. (Blood. 2010;116(9):1422-1432)