Brain pericytes serve as microglia-generating multipotent vascular stem cells following ischemic stroke.
Brain pericytes serve as microglia-generating multipotent vascular stem cells following ischemic stroke.
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DOI：
10.1186/s12974-016-0523-9
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发表时间：
2016-03-07
影响因子：
9.3
通讯作者：
Nakagomi T
中科院分区：
文献类型：
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作者：
Sakuma R;Kawahara M;Nakano-Doi A;Takahashi A;Tanaka Y;Narita A;Kuwahara-Otani S;Hayakawa T;Yagi H;Matsuyama T;Nakagomi T
小胶质细胞是中枢神经系统（CNS）的常驻巨噬细胞群体，并发挥着重要作用，特别是在炎症介导的病理状况（例如缺血性中风）中。越来越多的证据表明，位于血管周围的血管细胞群，而不是循环细胞，含有干细胞，并且这些驻留的血管干细胞（VSCs）可能是一些小胶质细胞的来源。然而，这些细胞在病理性CNS条件下的确切特征和起源仍不清楚。在这项研究中，我们使用小鼠脑梗死模型，以调查是否反应性周细胞（PC）获得小胶质细胞产生的VSC活动缺血。我们证明了本地化的离子钙结合衔接分子1（Iba 1）表达小胶质细胞的血管周围区域内缺血区。这些细胞表达血小板衍生生长因子受体-β（PDGFRβ），这是血管PC的标志。从缺血区域而非非缺血区域分离的PDGFRβ+ PC表达干细胞/未分化细胞标志物，随后分化为各种细胞类型，包括具有吞噬能力的小胶质细胞样细胞。研究结果表明，血管PC在病理条件下获得多能VSC活性，因此可能是小胶质细胞的新来源。本文的在线版本（doi：10.1186/s12974-016-0523-9）包含补充材料，可供授权用户使用。
Microglia are the resident macrophage population of the central nervous system (CNS) and play essential roles, particularly in inflammation-mediated pathological conditions such as ischemic stroke. Increasing evidence shows that the population of vascular cells located around the blood vessels, rather than circulating cells, harbor stem cells and that these resident vascular stem cells (VSCs) are the likely source of some microglia. However, the precise traits and origins of these cells under pathological CNS conditions remain unclear. In this study, we used a mouse model of cerebral infarction to investigate whether reactive pericytes (PCs) acquire microglia-producing VSC activity following ischemia. We demonstrated the localization of ionized calcium-binding adaptor molecule 1 (Iba1)-expressing microglia to perivascular regions within ischemic areas. These cells expressed platelet-derived growth factor receptor-β (PDGFRβ), a hallmark of vascular PCs. PDGFRβ+ PCs isolated from ischemic, but not non-ischemic, areas expressed stem/undifferentiated cell markers and subsequently differentiated into various cell types, including microglia-like cells with phagocytic capacity. The study results suggest that vascular PCs acquire multipotent VSC activity under pathological conditions and may thus be a novel source of microglia. The online version of this article (doi:10.1186/s12974-016-0523-9) contains supplementary material, which is available to authorized users.