Brain pericytes acquire a microglial phenotype after stroke.
Pericytes are located on the abluminal side of endothelial cells lining the microvasculature in all organs. They have been identified as multipotent progenitor cells in several tissues of the body including the human brain. New evidence suggests that pericytes contribute to tissue repair, but their role in the injured brain is largely unknown. Here, we investigate the role of pericytes in ischemic stroke. Using a pericyte-reporter mouse model, we provide unique evidence that regulator of G-protein signaling 5 expressing cells are activated pericytes that leave the blood vessel wall, proliferate and give rise to microglial cells after ischemic brain injury. Consistently, we show that activated pericytes express microglial markers in human stroke brain tissue. We demonstrate that human brain-derived pericytes adopt a microglial phenotype and upregulate mRNA specific for activated microglial cells under hypoxic conditions in vitro. Our study indicates that the vasculature is a novel source of inflammatory cells with a microglial phenotype in brain ischemia and hence identifies pericytes as an important new target for the development of future stroke therapies.
Translational Neurology Group, Department of Clinical Science, Wallenberg Neuroscience Center, Lund University, 22184, Lund, Sweden.
Ilknur
I
Özen
Tomas
T
Deierborg
Kenichi
K
Miharada
Thomas
T
Padel
Elisabet
E
Englund
Guillem
G
Genové
Gesine
G
Paul
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D005947:Glucose / Q000172:deficiency; D006801:Humans; D019751:Intramolecular Transferases / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020286:Pericytes / Q000473:pathology*; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism; D020521:Stroke / Q000473:pathology*; D013997:Time Factors
C491049:Aif1 protein, mouse; D015703:Antigens, CD; D029681:Arabidopsis Proteins; D002135:Calcium-Binding Proteins; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D020710:RGS Proteins; C105346:Rgs5 protein, mouse; D019751:Intramolecular Transferases; C568454:marneral synthase, Arabidopsis; D005947:Glucose