Cytokine-induced differentiation of hematopoietic cells into microglia-like cells in?vitro
Cytokine-induced differentiation of hematopoietic cells into microglia-like cells in?vitro
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细胞因子诱导造血细胞体外分化为小胶质细胞样细胞
DOI：
10.1111/cen3.12429
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发表时间：
2018
影响因子：
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通讯作者：
Shimizu Toshiaki
中科院分区：
文献类型：
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作者：
Igarashi Ayuko;Sakuma Hiroshi;Hayashi Masaharu;Noto Daisuke;Miyake Sachiko;Okumura Akihisa;Shimizu Toshiaki
目的小胶质细胞是中枢神经系统的免疫细胞。虽然小胶质细胞完全来自卵黄囊祖细胞，但一些研究表明，造血细胞在某些条件下具有在CNS中分化为小胶质细胞的潜力。几种体外方法已被报道，以诱导形成的小胶质细胞从造血细胞，使用粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-34（IL-34）。MethodsMurine bone marrow lineage-negative（BMLN）细胞与星形胶质细胞共培养一周，在存在或不存在的集落刺激因子。结果BMLN细胞与星形胶质细胞共培养后可分化为小胶质细胞样细胞（CD 11b + CD 45 lo F4/80 lo CX 3CR 1 hi），其表面标志物的表达模式与骨髓源性巨噬细胞（CD 11b + CD 45 hi F4/80 hi CX 3CR 1 lo）不同。形态学上，小胶质细胞样细胞被发现具有积极的延伸和收缩长分支的过程。此外，发现这些细胞在分化过程中显着增殖，这取决于CSF 1受体（CSF 1 R）信号传导。巨噬细胞集落刺激因子（M-CSF）或GM-CSF诱导BMLN细胞分化为不同于小胶质细胞的CD 11b hi CD 45 hi细胞。相比之下，IL-34诱导分化为具有相对较高CX 3CR 1表达的CD 11b + CD 45 lo小胶质样细胞。虽然TGF-β不能诱导具有突起形态的小胶质样细胞的形成，
ObjectivesMicroglia are the immune cells of the central nervous system (CNS). Although microglia exclusively arise from yolk sac progenitors, some studies suggest that hematopoietic cells have the potential to differentiate into microglia in the CNS under certain conditions. Several in vitro methods have been reported to induce the formation of microglia from hematopoietic cells, using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-34 (IL-34).MethodsMurine bone marrow lineage-negative (BMLN) cells co-cultured with astrocytes for one week in the presence or absence of colony stimulating factors. Surface markers for microglia were examined by flow cytometry.ResultsBMLN cells co-cultured with astrocytes developed into microglia-like cells (CD11b+ CD45 lo F4/80 lo CX3CR1 hi), whose expression pattern of surface markers was distinct from bone-marrow-derived macrophages (CD11b+ CD45 hi F4/80 hi CX3CR1 lo). Morphologically, microglia-like cells were found to possess actively extending and retracting long branched processes. Additionally, these cells were found to proliferate significantly during differentiation and this was dependent on CSF1 receptor (CSF1R) signaling. Macrophage colony-stimulating factor (M-CSF) or GM-CSF induced the differentiation of BMLN cells into CD11b hi CD45 hi cells that were different from microglia. In contrast, IL-34 induced differentiation into CD11b+ CD45 lo microglia-like cells with relatively higher CX3CR1 expression. Although TGF-beta failed to induce the formation of microglia-like cells with process-bearing morphology, BMLN cells