Developmental stages of myeloid dendritic cells in mouse bone marrow
Developmental stages of myeloid dendritic cells in mouse bone marrow
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DOI：
10.1093/intimm/dxg050
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发表时间：
2003-04-01
影响因子：
4.4
通讯作者：
Leenen, PJM
中科院分区：
文献类型：
--
作者：
Nikolic, T;de Bruijn, MFTR;Leenen, PJM
树突状细胞（DC）与其他造血细胞类型的谱系关系已被广泛研究，导致鉴定出产生不同DC类型的不同骨髓（BM）祖细胞。然而，BM中DC前体的不同成熟阶段的身份仍然不清楚。在这项研究中，我们定义了小鼠骨髓中髓样DC谱系的体内发育步骤。为此，根据BM细胞的CD31（ER-MP12）、Ly-6C（ER-MP20）和ER-MP58抗原的表达来分离BM细胞，并使用粒细胞巨噬细胞集落刺激因子作为特异性生长因子来刺激BM细胞发育成髓样DC。DC由三个BM亚群发展而来：ER-MP12 */20（-）（早期母细胞）、ER-MP12 */20（+）（髓样母细胞）和ER-MP12（-）/20（hi）（单核细胞）。体外发育的DC的动力学和表型特征表明，这三个群体代表了髓样DC前体的连续成熟阶段。在最早的ER-MP12（hi）/20（-）人群中，DC前体仅发生在骨髓限制性ER-MP58（hi）亚组中。通过使用开关培养，我们表明，这些BM前体亚群，当刺激发展成巨噬细胞使用巨噬细胞集落刺激因子，保留发展成髓样DC的能力，直到成熟的高级阶段。总之，这些发现支持巨噬细胞和髓样DC在其BM发育过程中的共同ER-MP12/20定义的分化途径。
The lineage relationship of dendritic cells (DC) with other hematopoietic cell types has been studied extensively, resulting in the identification of different bone marrow (BM) progenitors that give rise to distinct DC types. However, the identity of the different maturation stages of DC precursors in the BM remains unclear. In this study we define the in vivo developmental steps of the myeloid DC lineage in mouse BM. To this end, BM cells were separated according to their expression of CD31 (ER-MP12), Ly-6C (ER-MP20) and ER-MP58 antigens, and stimulated to develop into myeloid DC, using granulocyte macrophage colony stimulating factor as a specific growth factor. DC developed from three BM subpopulations: ER-MPhi/20(-) (early blast cells), ER-MP12*/20(+) (myeloid blasts) and ER-MP12(-)/20(hi) (monocytes). The kinetic and phenotypic features of DC developing in vitro indicate that the three populations represent successive maturation stages of myeloid DC precursors. Within the earliest ER-MP12(hi)/20(-) population; DC precursors exclusively occurred in the myeloid-restricted ER-MP58(hi) subset. By using switch cultures, we show that these BM precursor subpopulations, when stimulated to develop into macrophages using macrophage colony stimulating factor, retain the ability to develop into myeloid DC until advanced stages of maturation. Together, these findings support a common ER-MP12/20-defined differentiation pathway for both macrophages and myeloid DC throughout their BM development.