title: Injury Leads to the Appearance of Cells with Characteristics of Both Microglia and Astrocytes in Mouse and Human Brain.
abstract: Microglia and astrocytes have been considered until now as cells with very distinct identities. Here, we assessed the heterogeneity within microglia/monocyte cell population in mouse hippocampus and determined their response to injury, by using single-cell gene expression profiling of cells isolated from uninjured and deafferented hippocampus. We found that in individual cells, microglial markers Cx3cr1, Aif1, Itgam, and Cd68 were co-expressed. Interestingly, injury led to the co-expression of the astrocyte marker Gfap in a subpopulation of Cx3cr1-expressing cells from both the injured and contralesional hippocampus. Cells co-expressing astrocyte and microglia markers were also detected in the in vitro LPS activation/injury model and in sections from human brain affected by stroke, Alzheimer's disease, and Lewy body dementia. Our findings indicate that injury and chronic neurodegeneration lead to the appearance of cells that share molecular characteristics of both microglia and astrocytes, 2 cell types with distinct embryologic origin and function.
authors.affiliation: Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Wilhelmsson
authors.affiliation: Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Andersson
authors.affiliation: Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: de Pablo
authors.affiliation: Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Roy
authors.initials: R
authors.lastname: Pekny
authors.affiliation: Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 405 30 Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Ståhlberg
authors.affiliation: Science for Life Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Mulder
authors.affiliation: Science for Life Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mitsios
authors.affiliation: Division of Neuropathology, Institute of Pathology, Faculty of Medicine, University of Debrecen, Hungary.|Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.
authors.forename: Tibor
authors.initials: T
authors.lastname: Hortobágyi
authors.affiliation: Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 405 30 Gothenburg, Sweden.|Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.|Hunter Medical Research Institute, University of Newcastle, New South Wales, Australia.
authors.forename: Milos
authors.initials: M
authors.lastname: Pekny
authors.affiliation: Laboratory of Regenerative Neuroimmunology, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, 405 30 Gothenburg, Sweden.|Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.|Hunter Medical Research Institute, University of Newcastle, New South Wales, Australia.
authors.forename: Marcela
authors.initials: M
authors.lastname: Pekna
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D000818:Animals; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology*; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1 / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D003704:Dementia / Q000473:pathology; D018728:Entorhinal Cortex / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D039481:CD11b Antigen; D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D005947:Glucose
keywords: AIF1; Alzheimer's disease; C1q; CCR2; CX3CR1; Lewy body dementia; glial fibrillary acidic protein; single cell gene expression; stroke