title: Brain pericytes serve as microglia-generating multipotent vascular stem cells following ischemic stroke.
abstract: BACKGROUND
  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.
  
  
  METHODS
  In this study, we used a mouse model of cerebral infarction to investigate whether reactive pericytes (PCs) acquire microglia-producing VSC activity following ischemia.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The study results suggest that vascular PCs acquire multipotent VSC activity under pathological conditions and may thus be a novel source of microglia.
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. sakuma27@hyo-med.ac.jp.
authors.forename: Rika
authors.initials: R
authors.lastname: Sakuma
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. ma1tty0n.529@gmail.com.|Graduate School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan. ma1tty0n.529@gmail.com.
authors.forename: Maiko
authors.initials: M
authors.lastname: Kawahara
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. nakano@hyo-med.ac.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakano-Doi
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. ai01201216@gmail.com.|Graduate School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan. ai01201216@gmail.com.
authors.forename: Ai
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. giulietta.red.99@gmail.com.|Department of Neurosurgery, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. giulietta.red.99@gmail.com.
authors.forename: Yasue
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. ayatomo11190403@yahoo.co.jp.
authors.forename: Aya
authors.initials: A
authors.lastname: Narita
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. sachik@hyo-med.ac.jp.
authors.forename: Sachi
authors.initials: S
authors.lastname: Kuwahara-Otani
authors.affiliation: Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. tetsu@hyo-med.ac.jp.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Hayakawa
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. h-yagi@hyo-med.ac.jp.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Yagi
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. tomohiro@hyo-med.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuyama
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo, 663-8501, Japan. nakagomi@hyo-med.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagomi
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D002544:Cerebral Infarction / Q000473:pathology; D008297:Male; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D020286:Pericytes / Q000378:metabolism / Q000473:pathology*; D010587:Phagocytosis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D020521:Stroke / Q000473:pathology*
chemical_list: D020797:Receptor, Platelet-Derived Growth Factor beta