Characterization of microglia induced from mouse embryonic stem cells and their migration into the brain parenchyma
Autor: | Akira Tominaga, Kae Chang Park, Keiji Shimizu, Takahiro Tsuchiya, Eiichi Nakai, Shoko M. Yamada, Masato Furuya, Hiromichi Nakabayashi, Shinichi Toyonaga, Naoki Ikawa |
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Rok vydání: | 2004 |
Předmět: |
Immunology
Green Fluorescent Proteins Mice Transgenic Cell Line Mice Antigens CD Cell Movement medicine Immunology and Allergy Animals Lymph node CD86 CD40 Microglia biology Macrophages Stem Cells Histocompatibility Antigens Class I Histocompatibility Antigens Class II Brain Cell Differentiation Embryo Mammalian Embryonic stem cell Cell biology Transplantation Mice Inbred C57BL medicine.anatomical_structure nervous system Neurology Cell culture Antigens Surface Injections Intravenous biology.protein Female Neurology (clinical) CD80 Stem Cell Transplantation |
Zdroj: | Journal of neuroimmunology. 160(1-2) |
ISSN: | 0165-5728 |
Popis: | We derived microglia from mouse embryonic stem cells (ES cells) at very high density. Using the markers Mac1(+)/CD45(low) and Mac1(+)/CD45(high) to define microglia and macrophages, respectively, we show that Mac1(+) cells are induced by GM-CSF stimulation following neuronal differentiation of mouse ES cells using a five-step method. CD45(low) expression was high and CD45(high) expression was low on induced cells. We used a density gradient method to obtain a large amount of microglia-like cells, approximately 90% of Mac1(+) cells. Microglia-like cells expressed MHC class I, class II, CD40, CD80, CD86, and IFN-gammaR. The expression level of these molecules on microglia-like cells was barely enhanced by IFN-gamma. Intravenously transferred GFP(+) microglia derived from GFP(+) ES cells selectively accumulated in brain but not in peripheral tissues such as spleen and lymph node. GFP(+) cells were detected mainly in corpus callosum and hippocampus but were rarely seen in cerebral cortex, where Iba1, another marker of microglia, is primarily expressed. Furthermore, both GFP(+) and Iba1(+) cells exhibited a ramified morphology characteristic of mature microglia. These studies suggest that ES cell-derived microglia-like cells obtained using our protocol are functional and migrate selectively into the brain but not into peripheral tissues after intravenous transplantation. |
Databáze: | OpenAIRE |
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