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Diverse Requirements for Microglial Survival, Specification, and Function Revealed by Defined-Medium Cultures

机译:鉴定中等文化揭示的微胶质存活率,规格和功能多样化要求

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摘要

Microglia, the resident macrophages of the CNS, engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-beta 2, and cholesterol. Using microglial cultures that have never been exposed to serum, we demonstrate a dramatic and lasting change in phagocytic capacity after serum exposure. Finally, we find that mature microglia rapidly lose signature gene expression after isolation, and that this loss can be reversed by engrafting cells back into an intact CNS environment. These data indicate that the specialized gene expression profile of mature microglia requires continuous instructive signaling from the intact CNS.
机译:Microglia是CNS的常规巨额,从事各种CNS特定功能,对开发和健康至关重要。为了更好地研究微胶质细胞和将它们与其他组织巨噬细胞群体区分开的性质,我们优化了无血清培养条件,以允许在培养基条件下允许高度分枝的成人微胶质的生存。我们发现星形胶质细胞衍生的因素预防小体内死亡,并且该活性由三个主要成分,CSF-1 / IL-34,TGF-β2和胆固醇产生。使用从未暴露于血清的微胶质培养物,我们证明了血清暴露后吞噬能力的显着和持久变化。最后,我们发现成熟的微胶质细胞在分离后迅速失去签名基因表达,并且通过将细胞恢复到完整的CNS环境中,可以将这种损失逆转。这些数据表明,成熟微胶质细胞的专用基因表达谱需要来自完整的CNS的连续指示信号。

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