title: Identification of a unique TGF-β-dependent molecular and functional signature in microglia.
abstract: Microglia are myeloid cells of the CNS that participate both in normal CNS function and in disease. We investigated the molecular signature of microglia and identified 239 genes and 8 microRNAs that were uniquely or highly expressed in microglia versus myeloid and other immune cells. Of the 239 genes, 106 were enriched in microglia as compared with astrocytes, oligodendrocytes and neurons. This microglia signature was not observed in microglial lines or in monocytes recruited to the CNS, and was also observed in human microglia. We found that TGF-β was required for the in vitro development of microglia that express the microglial molecular signature characteristic of adult microglia and that microglia were absent in the CNS of TGF-β1-deficient mice. Our results identify a unique microglial signature that is dependent on TGF-β signaling and provide insights into microglial biology and the possibility of targeting microglia for the treatment of CNS disease.
authors: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Oleg
authors: O
authors: Butovsky
authors: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
authors: Mark P
authors: MP
authors: Jedrychowski
authors: Neuroimmunology Unit, Montréal Neurological Institute, McGill University, Montréal, Québec, Canada.
authors: Craig S
authors: CS
authors: Moore
authors: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Ron
authors: R
authors: Cialic
authors: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Amanda J
authors: AJ
authors: Lanser
authors: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Galina
authors: G
authors: Gabriely
authors: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Thomas
authors: T
authors: Koeglsperger
authors: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Ben
authors: B
authors: Dake
authors: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Pauline M
authors: PM
authors: Wu
authors: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Camille E
authors: CE
authors: Doykan
authors: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Zain
authors: Z
authors: Fanek
authors: Department of Immunology, Cleveland Clinic, Cleveland, Ohio, USA.
authors: Liping
authors: L
authors: Liu
authors: Brain Science Institute and Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Zhuoxun
authors: Z
authors: Chen
authors: Brain Science Institute and Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Jeffrey D
authors: JD
authors: Rothstein
authors: Department of Immunology, Cleveland Clinic, Cleveland, Ohio, USA.
authors: Richard M
authors: RM
authors: Ransohoff
authors: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
authors: Steven P
authors: SP
authors: Gygi
authors: Neuroimmunology Unit, Montréal Neurological Institute, McGill University, Montréal, Québec, Canada.
authors: Jack P
authors: JP
authors: Antel
authors: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Howard L
authors: HL
authors: Weiner
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology*; D002852:Chromatography, Ion Exchange; D004622:Embryo, Mammalian; D005260:Female; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics; D017628:Microglia / Q000145:classification / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D046888:Tissue Array Analysis; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D035683:MicroRNAs; C553058:P2ry12 protein, rat; D058925:Receptors, Purinergic P2Y12; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1