Abstract
BackgroundMicroglia, as well as other tissue-resident macrophages, arise from yolk sac progenitors. Thus, it is likely that the central nervous system environment is critical for the acquisition of a distinct microglial phenotype. Several microRNAs that are enriched in the brain play crucial roles in brain development and may also play a role in the differentiation of microglia.MethodsTo track the differentiation of hematopoietic cells into microglia, lineage-negative bone marrow cells were co-cultured with astrocytes in the absence or presence of microRNAs or their inhibitors. Microglia-like cells were identified as small, round cells that were immunopositive for CD11b, Iba1, CX3CR1, and triggering receptor expressed on myeloid cells (TREM)-2.ResultsFive microRNAs (miR-101a, miR-139-3p, miR-214*, miR-218, and miR-1186) were identified as modifiers of the differentiation of bone marrow-derived microglia-like cells. Among them, miR-101a facilitated the differentiation of bone marrow cells into microglia-like cells most potently. Small, round cells expressing CD11b, Iba1, CX3CR1, and TREM-2 were predominant in cells treated by miR-101a. miR-101a was abundantly expressed in non-microglial brain cells. Transfection of miR-101a into microglia significantly increased the production of IL-6 in response to LPS. Finally, miR-101a downregulated the expression of MAPK phosphatase-1.ConclusionsmiR-101a, which is enriched in the brain, promotes the differentiation of bone marrow cells into microglia-like cells.
Highlights
Microglia, as well as other tissue-resident macrophages, arise from yolk sac progenitors
Identification of miR-101a as a modulator of microglial morphology by miRNA inhibitor library screening We speculated that secreted factors including miRNAs induced the differentiation of microglia-like cells
In order to screen miRNAs that affect microglial development, green fluorescence protein (GFP)+LN− cells were co-cultured with astrocytes and were treated with an miRNA inhibitor library
Summary
As well as other tissue-resident macrophages, arise from yolk sac progenitors. MiRNAs are enriched in the central nervous system (CNS) and play crucial roles in the development and plasticity of the brain [2]. A recent study demonstrated that other tissue-resident macrophages originate from yolk sac progenitors [8]. This evidence suggests that the developmental fate of tissue macrophages is influenced by the environment in which cells are placed. In addition to colony-stimulating factors including interleukin-34, which dictate the developmental fate of microglia [9], miRNAs enriched in the CNS may play a role in the acquisition of a distinct microglial phenotype. We developed an in vitro model in which lineage-negative bone marrow cells co-cultured with astrocytes differentiated into microglia-like cells [11, 12]
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