Abstract
BackgroundMicroglia 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.MethodsIn this study, we used a mouse model of cerebral infarction to investigate whether reactive pericytes (PCs) acquire microglia-producing VSC activity following ischemia.ResultsWe 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.ConclusionsThe study results suggest that vascular PCs acquire multipotent VSC activity under pathological conditions and may thus be a novel source of microglia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0523-9) contains supplementary material, which is available to authorized users.
Highlights
Microglia are the resident macrophage population of the central nervous system (CNS) and play essential roles, in inflammation-mediated pathological conditions such as ischemic stroke
Mounting evidence suggests that progenitor cells localized to the adventitia (adventitial progenitor cells (APCs)) around the blood vessels may serve as multipotent resident vascular stem cells (VSCs) [9] that contribute to vasculogenesis [10,11,12]
platelet-derived growth factor receptor-β (PDGFRβ)+ cells at the ischemic core and peri-ischemic areas rarely express CD68 on post-stroke days 5 (Additional file 4: Figure S3M–P) and 7 (Additional file 4: Figure S3Q–T). These findings were consistent with a previous report showing that regulator of G-protein signaling 5 (RGS5)+ PCs following ischemic stroke express ionized calcium-binding adaptor molecule 1 (Iba1) but not CD68 [36]. These results suggest that Iba1+ microglia that appear following ischemia are most likely not derived from perivascular macrophages
Summary
Microglia are the resident macrophage population of the central nervous system (CNS) and play essential roles, in inflammation-mediated pathological conditions such as ischemic stroke. Previous studies have demonstrated that microglia originate from progenitor cells in the embryonic yolk sac during early development and that embryonically derived microglia self-maintain until adulthood under normal conditions [3, 4] It remains unclear whether these cells can continuously produce microglia in the adult CNS, even under pathological conditions. PCs exhibit the potential for differentiation into multiple different cell populations, including neural cells, adipocytes, Sakuma et al Journal of Neuroinflammation (2016) 13:57 chondroblasts, and osteoblasts [15, 16] It remains controversial whether PCs can produce microglia [17,18,19], we recently demonstrated that PCs acquire multipotent stem cell activity in response to brain injuries such as ischemia/hypoxia and that these reactive PCs can differentiate into various lineages, including the neural and vasculogenic lineages [20]. These findings led us to hypothesize that resident microglia might originate from ischemia-induced multipotent PCs following CNS injury
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