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Detection of MicroRNAs in Microglia by Real-time PCR in Normal CNS and During Neuroinflammation
Published on: July 23, 2012
MicroRNA-101a regulates microglial morphology and inflammation
Reiko Saika1,2,3, Hiroshi Sakuma1,3, Daisuke Noto1,4
1Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi-cho, Kodaira, Tokyo, Japan.
Background:
Microglia, 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.
Methods:
To 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.
Results:
Five 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.
Conclusions:
miR-101a, which is enriched in the brain, promotes the differentiation of bone marrow cells into microglia-like cells.
Insights
Brain microRNAs influence microglial cell development. Specifically, miR-101a promotes the differentiation of bone marrow cells into microglia-like cells, impacting brain immune cell populations.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Microglia, the brain's resident immune cells, originate from yolk sac progenitors.
- The central nervous system environment is crucial for developing a unique microglial phenotype.
- Brain-enriched microRNAs (miRNAs) are implicated in brain development and potentially microglial differentiation.
Purpose of the Study:
- To investigate the role of specific microRNAs in the differentiation of hematopoietic cells into microglia-like cells.
- To identify key microRNAs that modulate microglial development in the central nervous system.
Main Methods:
- Co-culture of lineage-negative bone marrow cells with astrocytes, with or without specific microRNAs or inhibitors.
- Identification of microglia-like cells based on immunopositivity for CD11b, Iba1, CX3CR1, and TREM-2.
- Assessment of miR-101a's effect on microglia-like cell differentiation and function, including IL-6 production and MAPK phosphatase-1 expression.
Main Results:
- Five microRNAs (miR-101a, miR-139-3p, miR-214*, miR-218, miR-1186) were identified as modifiers of microglia-like cell differentiation.
- miR-101a demonstrated the most potent facilitation of bone marrow cell differentiation into microglia-like cells.
- miR-101a transfection into microglia increased IL-6 production in response to LPS and downregulated MAPK phosphatase-1 expression.
Conclusions:
- miR-101a, a brain-enriched microRNA, significantly promotes the differentiation of bone marrow cells into microglia-like cells.
- This finding highlights the role of specific microRNAs in shaping microglial identity and function within the brain.
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