The transcription factor PU.1 is critical for viability and function of human brain microglia.

Abstract:

:Microglia are the predominant resident immune cells of the brain and can assume a range of phenotypes. They are critical for normal brain development and function but can also contribute to many disease processes. Although they are widely studied, the transcriptional control of microglial phenotype and activation requires further research. PU.1 is a key myeloid transcription factor expressed by peripheral macrophages and rodent microglia. In this article, we report the presence of PU.1 specifically in microglia of the adult human brain and we examine its functional role in primary human microglia. Using siRNA, we achieved substantial PU.1 protein knock-down in vitro. By assessing a range of characteristic microglial proteins we found decreased viability of adult human microglia with reduced PU.1 protein expression. This observation was confirmed with PU.1 antisense DNA oligonucleotides. An important function of microglia is to clear debris by phagocytosis. We assessed the impact of loss of PU.1 on microglial phagocytosis and show that PU.1 siRNA reduces the ability of adult human microglia to phagocytose amyloid-beta1-42 peptide. These results show that PU.1 controls human microglial viability and function and suggest PU.1 as a molecular target for manipulation of human microglial phenotype.

journal_name

Glia

journal_title

Glia

authors

Smith AM,Gibbons HM,Oldfield RL,Bergin PM,Mee EW,Faull RL,Dragunow M

doi

10.1002/glia.22486

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

929-42

issue

6

eissn

0894-1491

issn

1098-1136

journal_volume

61

pub_type

杂志文章

相关文献

GLIA文献大全
  • Microglia as modulators of cognition and neuropsychiatric disorders.

    abstract::It has become evident recently only that microglia are not only responsible for immunomodulatory functions in the brain but represent vital components of the larger synaptic formation, which also includes pre and postsynaptic neurones as well as astrocytes. Microglia critically contribute to CNS homeostasis by their a...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.22372

    authors: Blank T,Prinz M

    更新日期:2013-01-01 00:00:00

  • Compromised blood-nerve barrier, astrogliosis, and myelin disruption in optic nerves during fatal murine cerebral malaria.

    abstract::We examined the optic nerve, as an analogous tissue to brain white matter, to assess possible relationships between changes in the blood-nerve barrier, axonal integrity, and astrocyte morphology in the central nervous system during fatal murine cerebral malaria (FMCM). In the FMCM model, namely, CBA mice infected with...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-1136(199702)19:2<135::aid-glia5

    authors: Ma N,Madigan MC,Chan-Ling T,Hunt NH

    更新日期:1997-02-01 00:00:00

  • Trimethyltin-induced expression of GABA and vimentin immunoreactivities in astrocytes of the rat brain.

    abstract::Adult Sprague-Dawley rats were given a single dose of trimethyltin chloride (TMT). Three days following treatment, a neuronal alteration was observed in the CA3c pyramidal cell layer of hippocampus which was not accompanied by any apparent astrocyte reaction. At 1 as well as 2 weeks after treatment, a gliosis in hippo...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440110410

    authors: Andersson H,Luthman J,Olson L

    更新日期:1994-08-01 00:00:00

  • Effect of elevated K(+), hypotonic stress, and cortical spreading depression on astrocyte swelling in GFAP-deficient mice.

    abstract::Glial fibrillary acidic protein (GFAP) is the main component of intermediate filaments in astrocytes. To assess its function in astrocyte swelling, we compared astrocyte membrane properties and swelling in spinal cord slices of 8- to 10-day-old wild-type control (GFAP(+/+)) and GFAP-knockout (GFAP(-/-)) mice. Membrane...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.1084

    authors: Anderová M,Kubinová S,Mazel T,Chvátal A,Eliasson C,Pekny M,Syková E

    更新日期:2001-09-01 00:00:00

  • Ultrastructural study of phagocytic activities of young astrocytes in injured neonatal rat brain following intracerebral injection of colloidal carbon.

    abstract::The cellular reaction to injury in the mature central nervous system (CNS) has been extensively studied in both man and animals, while a detailed study of the reaction of the immature CNS to injury is lacking in the literature. This study was undertaken to elucidate the response of young astrocytes following injection...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440010306

    authors: Al-Ali SY,Al-Zuhair AG,Dawod B

    更新日期:1988-01-01 00:00:00

  • Neurotrophin-3 targets the translational initiation machinery in oligodendrocytes.

    abstract::Neurotrophin-3 (NT-3) regulates oligodendrocyte (OLG) differentiation by mechanisms that remain poorly understood. Exposure of OLGs to NT-3 induces a significant increase in the levels of myelin basic protein (MBP). However, we found that this stimulation occurs in the absence of measurable effects on MBP gene promote...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20888

    authors: Coelho RP,Yuelling LM,Fuss B,Sato-Bigbee C

    更新日期:2009-12-01 00:00:00

  • Expression of beta-adrenergic receptors by astrocytes isolated from adult rat cortex.

    abstract::Astrocytes are the most numerous cell type in the central nervous system. When cultured, these cells express a wide variety of receptors for neurotransmitters. Nonetheless, it has yet to be firmly established that adult astrocytes in situ express receptors for neurotransmitters. In this report the technique of combine...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440020507

    authors: Salm AK,McCarthy KD

    更新日期:1989-01-01 00:00:00

  • Production, characterization, and efficient transfection of highly pure oligodendrocyte precursor cultures from mouse embryonic neural progenitors.

    abstract::Much current knowledge of oligodendrocyte biology, the myelin-forming cells in the central nervous system, comes from cell culture studies mainly from postnatal rat tissue but mouse cells have been much more difficult to produce in large quantities. We have developed a high yield protocol for production of oligodendro...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20702

    authors: Pedraza CE,Monk R,Lei J,Hao Q,Macklin WB

    更新日期:2008-09-01 00:00:00

  • Embryonic macrophages and microglia ablation alter the development of dorsal root ganglion sensory neurons in mouse embryos.

    abstract::Microglia are known to regulate several aspects of the development of the central nervous system. When microglia colonize the spinal cord, from E11.5 in the mouse embryo, they interact with growing central axons of dorsal root ganglion sensory neurons (SNs), which suggests that they may have some functions in SN devel...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23499

    authors: Angelim MKSC,Maia LMSS,Mouffle C,Ginhoux F,Low D,Amancio-Dos-Santos A,Makhoul J,Le Corronc H,Mangin JM,Legendre P

    更新日期:2018-11-01 00:00:00

  • PPARβ/δ-agonist GW0742 ameliorates dysfunction in fatty acid oxidation in PSEN1ΔE9 astrocytes.

    abstract::Astrocytes are the gatekeepers of neuronal energy supply. In neurodegenerative diseases, bioenergetics demand increases and becomes reliant upon fatty acid oxidation as a source of energy. Defective fatty acid oxidation and mitochondrial dysfunctions correlate with hippocampal neurodegeneration and memory deficits in ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23534

    authors: Konttinen H,Gureviciene I,Oksanen M,Grubman A,Loppi S,Huuskonen MT,Korhonen P,Lampinen R,Keuters M,Belaya I,Tanila H,Kanninen KM,Goldsteins G,Landreth G,Koistinaho J,Malm T

    更新日期:2019-01-01 00:00:00

  • Transcriptional regulation of homeostatic and disease-associated-microglial genes by IRF1, LXRβ, and CEBPα.

    abstract::Microglia transform from homeostatic to disease-associated-microglia (DAM) profiles in neurodegeneration. Within DAM, we recently identified distinct pro-inflammatory and anti-inflammatory sub-profiles although transcriptional regulators of homeostatic and distinct DAM profiles remain unclear. Informed by these studie...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23678

    authors: Gao T,Jernigan J,Raza SA,Dammer EB,Xiao H,Seyfried NT,Levey AI,Rangaraju S

    更新日期:2019-10-01 00:00:00

  • Inducible gene expression in GFAP+ progenitor cells of the SGZ and the dorsal wall of the SVZ-A novel tool to manipulate and trace adult neurogenesis.

    abstract::In the adult mammalian brain, neurogenesis originates from astrocyte-like stem cells. We generated a transgenic mouse line in which the tetracycline dependent transactivator (tTA) is expressed under the control of the murine GFAP promoter. In this mouse line, inducible gene expression targets virtually all GFAP-expres...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.21129

    authors: Weber T,Baier V,Pauly R,Sahay A,Baur M,Herrmann E,Ciccolini F,Hen R,Kronenberg G,Bartsch D

    更新日期:2011-04-01 00:00:00

  • ERK1/2 signaling is essential for the chemoattraction exerted by human FGF2 and human anosmin-1 on newborn rat and mouse OPCs via FGFR1.

    abstract::Signaling through fibroblast growth factor receptors (FGFRs) is essential for many cellular processes including proliferation and migration, as well as differentiation events such as myelination. Anosmin-1 is an extracellular matrix (ECM) glycoprotein that interacts with the fibroblast growth factor receptor 1 (FGFR1)...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22609

    authors: Murcia-Belmonte V,Medina-Rodríguez EM,Bribián A,de Castro F,Esteban PF

    更新日期:2014-03-01 00:00:00

  • Proinflammatory cytokine regulation of cyclic AMP-phosphodiesterase 4 signaling in microglia in vitro and following CNS injury.

    abstract::Cyclic AMP suppresses immune cell activation and inflammation. The positive feedback loop of proinflammatory cytokine production and immune activation implies that cytokines may not only be regulated by cyclic AMP but also conversely regulate cyclic AMP. This study examined the effects of tumor necrosis factor (TNF)-α...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22401

    authors: Ghosh M,Garcia-Castillo D,Aguirre V,Golshani R,Atkins CM,Bramlett HM,Dietrich WD,Pearse DD

    更新日期:2012-12-01 00:00:00

  • Astrocytes, the rising stars of the glioblastoma microenvironment.

    abstract::Glioblastoma (GBM) is an aggressive primary tumor, causing thousands of deaths worldwide every year. The mean survival of patients with GBM remains below 20 months despite current available therapies. GBM cells' interactions with their stromal counterparts are crucial for tumor development. Astrocytes are glial cells ...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.23520

    authors: Brandao M,Simon T,Critchley G,Giamas G

    更新日期:2019-05-01 00:00:00

  • Spatial arrangement of microglia in the mouse hippocampus: a stereological study in comparison with astrocytes.

    abstract::Microglia are classically considered to be immune cells in the brain, but have now been proven to be involved in neuronal activity as well. Here we stereologically analyzed the spatial arrangement of microglia in the mouse hippocampus. First, we estimated the numerical densities (NDs) of microglia identified by ionize...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20552

    authors: Jinno S,Fleischer F,Eckel S,Schmidt V,Kosaka T

    更新日期:2007-10-01 00:00:00

  • Epidermal growth factor receptor expression regulates proliferation in the postnatal rat retina.

    abstract::Epidermal growth factor (EGF) is known to promote proliferation of both retinal progenitors and Muller glia in vitro, but several questions remain concerning an in vivo role for this factor. In this study, we investigated whether the EGF receptor (EGFR) is necessary for the maintenance of normal levels of progenitor a...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20361

    authors: Close JL,Liu J,Gumuscu B,Reh TA

    更新日期:2006-08-01 00:00:00

  • Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons: role of microglia.

    abstract::We recently showed that trisialoganglioside (GT1b) induces cell death of dopaminergic neurons in rat mesencephalic cultures (Chung et al., Neuroreport 12:611-614, 2001). The present study examines the in vivo neurotoxic effects of GT1b on dopaminergic neurons in the substantia nigra (SN) of Sprague-Dawley rats. Seven ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.10047

    authors: Ryu JK,Shin WH,Kim J,Joe EH,Lee YB,Cho KG,Oh YJ,Kim SU,Jin BK

    更新日期:2002-04-01 00:00:00

  • GLAST-CreERT2 mediated deletion of GDNF increases brain damage and exacerbates long-term stroke outcomes after focal ischemic stroke in mouse model.

    abstract::Focal ischemic stroke (FIS) is a leading cause of human death. Glial scar formation largely caused by reactive astrogliosis in peri-infarct region (PIR) is the hallmark of FIS. Glial cell-derived neurotrophic factor (GDNF) was originally isolated from a rat glioma cell-line supernatant and is a potent survival neurotr...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23848

    authors: Zhang N,Zhang Z,He R,Li H,Ding S

    更新日期:2020-11-01 00:00:00

  • Inhibition of inflammatory cells delays retinal degeneration in experimental retinal vein occlusion in mice.

    abstract::The role of microglia in retinal inflammation is still ambiguous. Branch retinal vein occlusion initiates an inflammatory response whereby resident microglia cells are activated. They trigger infiltration of neutrophils that exacerbate blood-retina barrier damage, regulate postischemic inflammation and irreversible lo...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23739

    authors: Jovanovic J,Liu X,Kokona D,Zinkernagel MS,Ebneter A

    更新日期:2020-03-01 00:00:00

  • Zn and Cu alteration in connection with astrocyte metallothionein I/II overexpression in the mouse brain upon physical stress.

    abstract::The distribution of metallothioneins I/II in the mouse brain and their specific area distribution upon physical stress were studied. To induce physical stress, groups of mice were subjected to total darkness for different periods (2 weeks, 1 month, and 2 months). The concentration of metallothioneins, evaluated by imm...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20020

    authors: Beltramini M,Di Pisa C,Zambenedetti P,Wittkowski W,Mocchegiani E,Musicco M,Zatta P

    更新日期:2004-07-01 00:00:00

  • ADAM-10 and ADAM-17 in the inflamed human CNS.

    abstract::Inflammatory demyelinating disorders of the CNS, such as multiple sclerosis (MS), are mediated, at least in part, by various cytokines and proteases. In the present study, we investigated the expression of A disintegrin and metalloproteinase (ADAM)-17, an important sheddase for various proteins, including tumor necros...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.10226

    authors: Kieseier BC,Pischel H,Neuen-Jacob E,Tourtellotte WW,Hartung HP

    更新日期:2003-06-01 00:00:00

  • Activation of interferon signaling pathways in spinal cord astrocytes from an ALS mouse model.

    abstract::Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting predominantly motor neurons. Recent studies suggest that the disease progression of ALS is non-cell-autonomous, although the interaction between neurons and glial cells in different disease stages is not entirely clear. Here, we ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.21167

    authors: Wang R,Yang B,Zhang D

    更新日期:2011-06-01 00:00:00

  • Pure astrocyte cultures derived from cells isolated from mature brain.

    abstract::Enriched preparations of oligodendrocytes, isolated either from adult bovine brain or from 30-day-old rat brain, eventually yield cultures in MEM-15% calf serum that contain, in addition to oligodendrocytes, proliferating astrocytes and variable numbers of fibroblast-like cells. If these cultures are switched to a ser...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440010608

    authors: Norton WT,Farooq M,Chiu FC,Bottenstein JE

    更新日期:1988-01-01 00:00:00

  • NOSH-aspirin (NBS-1120), a novel nitric oxide and hydrogen sulfide releasing hybrid, attenuates neuroinflammation induced by microglial and astrocytic activation: a new candidate for treatment of neurodegenerative disorders.

    abstract::Hydrogen sulfide (H2 S) and nitric oxide (NO) have been described as gasotransmitters. Anti-inflammatory activity in the central and peripheral nervous systems may be one of their functions. Previously we demonstrated that several SH(-) donors including H2 S-releasing aspirin (S-ASA) exhibited anti-inflammatory and ne...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22553

    authors: Lee M,McGeer E,Kodela R,Kashfi K,McGeer PL

    更新日期:2013-10-01 00:00:00

  • Phagocytosis of neuronal debris by microglia is associated with neuronal damage in multiple sclerosis.

    abstract::Neuroaxonal degeneration is a pathological hallmark of multiple sclerosis (MS) contributing to irreversible neurological disability. Pathological mechanisms leading to axonal damage include autoimmunity to neuronal antigens. In actively demyelinating lesions, myelin is phagocytosed by microglia and blood-borne macroph...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22276

    authors: Huizinga R,van der Star BJ,Kipp M,Jong R,Gerritsen W,Clarner T,Puentes F,Dijkstra CD,van der Valk P,Amor S

    更新日期:2012-03-01 00:00:00

  • Identification of Golli and myelin basic proteins in human brain during early development.

    abstract::The myelin basic protein gene (Mbp) encodes for the major myelin structural proteins and it is included in the Golli-Mbp gene complex. Previously, we observed MBP-like proteins in the human central nervous system (CNS) at developmental stages preceding myelination. In an effort to distinguish between Golli (HOG5 and H...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.10028

    authors: Tosic M,Rakic S,Matthieu J-,Zecevic N

    更新日期:2002-03-01 00:00:00

  • The origin of remyelinating cells in the adult central nervous system: the role of the mature oligodendrocyte.

    abstract::The sequence of events by which new oligodendrocytes are generated in the adult mammalian central nervous system has not been clearly defined. Here we review old evidence that remyelinating cells can arise from the division of mature oligodendrocytes. In addition, we report the results of a tissue culture study compar...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.440040214

    authors: Wood PM,Bunge RP

    更新日期:1991-01-01 00:00:00

  • Regulation of Schwann cell differentiation and proliferation by the Pax-3 transcription factor.

    abstract::Pax-3 is a paired domain transcription factor that plays many roles during vertebrate development. In the Schwann cell lineage, Pax-3 is expressed at an early stage in Schwann cells precursors of the embryonic nerve, is maintained in the nonmyelinating cells of the adult nerve, and is upregulated in Schwann cells afte...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22346

    authors: Doddrell RD,Dun XP,Moate RM,Jessen KR,Mirsky R,Parkinson DB

    更新日期:2012-09-01 00:00:00

  • Astrocytes protect neurons from neurotoxic injury by serum glutamate.

    abstract::Serum is used widely for culturing neurons and glial cells, and is thought to provide essential, albeit undefined, factors such as hormones, growth factors, and trace elements that promote the growth of cells in vitro. Moreover, serum can have profound effects on cell proliferation, differentiation, and cell morpholog...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-1136(199803)22:3<237::aid-glia3

    authors: Ye ZC,Sontheimer H

    更新日期:1998-03-01 00:00:00