2021
Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replication
2019
Mediation of the Acute Stress Response by the Skeleton
Berger JM, Singh P, Khrimian L, Morgan DA, Chowdhury S, Arteaga-Solis E, Horvath TL, Domingos AI, Marsland AL, Yadav V, Rahmouni K, Gao XB, Karsenty G. Mediation of the Acute Stress Response by the Skeleton. Cell Metabolism 2019, 30: 890-902.e8. PMID: 31523009, PMCID: PMC6834912, DOI: 10.1016/j.cmet.2019.08.012.Peer-Reviewed Original ResearchConceptsStress responseBony vertebratesAcute stress responseBone-derived signalsWild-type animalsGenetic studiesEndocrine mediationAdrenal insufficient patientsVertebratesOsteocalcinSympathetic toneParasympathetic neuronsWildOsteocalcin levelsStressorsTypes of stressorsSelective surgeOsteoblastsInactivationRodentsResponseGlutamateUptake
2018
The 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development
Tebbenkamp ATN, Varela L, Choi J, Paredes MI, Giani AM, Song JE, Sestan-Pesa M, Franjic D, Sousa AMM, Liu ZW, Li M, Bichsel C, Koch M, Szigeti-Buck K, Liu F, Li Z, Kawasawa YI, Paspalas CD, Mineur YS, Prontera P, Merla G, Picciotto MR, Arnsten AFT, Horvath TL, Sestan N. The 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development. Cell 2018, 175: 1088-1104.e23. PMID: 30318146, PMCID: PMC6459420, DOI: 10.1016/j.cell.2018.09.014.Peer-Reviewed Original ResearchConceptsCopy number variationsATP synthase dimersOxidative phosphorylation supercomplexesHuman neurodevelopmental disordersATP synthaseWS pathogenesisGene contributionMitochondrial featuresBrain developmentWilliams syndromeMitochondrial dysfunctionNeocortical pyramidal neuronsNeural phenotypesMitochondriaPyramidal neuronsMachineryMorphological featuresNeurodevelopmental disordersDysfunctionSupercomplexesPhenotype
2016
Bisphenol A influences oestrogen- and thyroid hormone-regulated thyroid hormone receptor expression in rat cerebellar cell culture.
Somogyi V, Horváth TL, Tóth I, Bartha T, Frenyó LV, Kiss DS, Jócsák G, Kerti A, Naftolin F, Zsarnovszky A. Bisphenol A influences oestrogen- and thyroid hormone-regulated thyroid hormone receptor expression in rat cerebellar cell culture. Acta Veterinaria Hungarica 2016, 64: 497-513. PMID: 27993100, DOI: 10.1556/004.2016.046.Peer-Reviewed Original ResearchComparison of Individual and Combined Effects of Four Endocrine Disruptors on Estrogen Receptor Beta Transcription in Cerebellar Cell Culture: The Modulatory Role of Estradiol and Triiodo-Thyronine
Jocsak G, Kiss DS, Toth I, Goszleth G, Bartha T, Frenyo LV, Horvath TL, Zsarnovszky A. Comparison of Individual and Combined Effects of Four Endocrine Disruptors on Estrogen Receptor Beta Transcription in Cerebellar Cell Culture: The Modulatory Role of Estradiol and Triiodo-Thyronine. International Journal Of Environmental Research And Public Health 2016, 13: 619. PMID: 27338438, PMCID: PMC4924076, DOI: 10.3390/ijerph13060619.Peer-Reviewed Original ResearchConceptsERβ mRNA expressionModulatory roleMRNA expressionCerebellar cell culturesGlial cellsEstrogen receptor β mRNA expressionEndocrine disruptorsAbsence of E2ED effectsPrimary cerebellar cell culturesΒ mRNA expressionAdverse health effectsHormonal milieuBody of evidenceHormone deficiencyCell culturesTriiodo-ThyronineHealth effectsEnvironmental substancesSimultaneous exposureEstradiolComparison of individualsObserved potencyE2T3Mitochondrial Uncoupling Protein 2 (UCP2) Regulates Retinal Ganglion Cell Number and Survival
Barnstable CJ, Reddy R, Li H, Horvath TL. Mitochondrial Uncoupling Protein 2 (UCP2) Regulates Retinal Ganglion Cell Number and Survival. Journal Of Molecular Neuroscience 2016, 58: 461-469. PMID: 26846222, PMCID: PMC4833669, DOI: 10.1007/s12031-016-0728-5.Peer-Reviewed Original ResearchConceptsRetinal ganglion cellsUncoupling protein 2Mitochondrial uncoupling protein 2Ganglion cellsRetinal ganglion cell numberNeurotrophic factor BDNFSurvival-promoting effectsGanglion cell numberUCP2 levelsRetinal neuron survivalProtein 2Critical developmental periodIntraocular injectionKainic acidNeuron survivalNeuronal survivalMouse retinaRetinal cellsElevated numbersAdult animalsSurvivalCell numberCell survivalImportant regulatorCell death
2015
Calcineurin Aγ is a Functional Phosphatase That Modulates Synaptic Vesicle Endocytosis*
Cottrell JR, Li B, Kyung JW, Ashford CJ, Mann JJ, Horvath TL, Ryan TA, Kim SH, Gerber DJ. Calcineurin Aγ is a Functional Phosphatase That Modulates Synaptic Vesicle Endocytosis*. Journal Of Biological Chemistry 2015, 291: 1948-1956. PMID: 26627835, PMCID: PMC4722470, DOI: 10.1074/jbc.m115.705319.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcineurinCells, CulturedEndocytosisHippocampusHumansMaleMiceMice, Inbred BALB CNeuronsRatsSynaptic VesiclesConceptsSynaptic vesicle cyclingVesicle cyclingHippocampal neuronsPsychiatric diseasesSynaptic vesicle endocytosisCultured rat hippocampal neuronsRNAi-mediated knockdownCalcineurin catalytic subunitRat hippocampal neuronsFunctional phosphataseCombination of immunocytochemistryVesicle endocytosisLow expression levelsCatalytic subunitPresynaptic substratePresynaptic terminalsPresynaptic functionΓ isoformsCalcineurin AαCatalytic isoformsImmuno-EMSpecific functionsExpression levelsMost tissuesPPP3CC
2012
Oligodendrocyte Regeneration after Neonatal Hypoxia Requires FoxO1-Mediated p27Kip1 Expression
Jablonska B, Scafidi J, Aguirre A, Vaccarino F, Nguyen V, Borok E, Horvath TL, Rowitch DH, Gallo V. Oligodendrocyte Regeneration after Neonatal Hypoxia Requires FoxO1-Mediated p27Kip1 Expression. Journal Of Neuroscience 2012, 32: 14775-14793. PMID: 23077062, PMCID: PMC3517297, DOI: 10.1523/jneurosci.2060-12.2012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornCell DifferentiationCells, CulturedCyclin-Dependent Kinase Inhibitor p27Forkhead Box Protein O1Forkhead Transcription FactorsGene Expression Regulation, DevelopmentalHumansHypoxia, BrainInfantInfant, NewbornMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutMice, TransgenicNerve RegenerationOligodendrogliaConceptsDiffuse white matter injuryNeonatal hypoxiaOligodendrocyte regenerationOligodendrocyte progenitor cell proliferationWhite matter injuryWhite matter lesionsPermanent neurodevelopmental disabilityCritical developmental time windowWhite matter developmentOverexpression of FoxO1Preterm infantsProgenitor cell proliferationDevelopmental time windowMatter lesionsOligodendrocyte deathAbnormal myelinationNeurodevelopmental disabilitiesMouse modelBiphasic effectP27Kip1 expressionNull miceOligodendrogenesisHypoxiaOligodendrocyte differentiationOligodendrocyte developmentUcp2 Induced by Natural Birth Regulates Neuronal Differentiation of the Hippocampus and Related Adult Behavior
Simon-Areces J, Dietrich MO, Hermes G, Garcia-Segura LM, Arevalo MA, Horvath TL. Ucp2 Induced by Natural Birth Regulates Neuronal Differentiation of the Hippocampus and Related Adult Behavior. PLOS ONE 2012, 7: e42911. PMID: 22905184, PMCID: PMC3414493, DOI: 10.1371/journal.pone.0042911.Peer-Reviewed Original ResearchConceptsUCP2 expressionCellular stressHippocampal neuronsChemical inhibitionMitochondrial bioenergeticsNeuronal differentiationGenetic ablationNatural birthProtein 2Adult behaviorCell proliferationCritical roleAdult brainNeuronal numberExpressionBioenergeticsNeuronsBirthDifferentiationRegulationProliferationSynaptogenesisVitroNeuroprotectionHippocampusModeling human cortical development in vitro using induced pluripotent stem cells
Mariani J, Simonini MV, Palejev D, Tomasini L, Coppola G, Szekely AM, Horvath TL, Vaccarino FM. Modeling human cortical development in vitro using induced pluripotent stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 12770-12775. PMID: 22761314, PMCID: PMC3411972, DOI: 10.1073/pnas.1202944109.Peer-Reviewed Original ResearchConceptsHuman brain developmentHuman induced pluripotent stem cellsLayer-specific cortical neuronsBrain developmentHuman cerebral cortexHuman cortical developmentStem cellsPluripotent stem cellsCerebral cortexCortical neuronsCortical developmentCNS regionsRadial gliaCortical wallDorsal telencephalonEmbryonic telencephalonGene expression profilesInduced pluripotent stem cellsIntermediate progenitorsTelencephalic developmentTelencephalonExpression profilesTranscriptional programsCellsGlia
2011
Cortical Glial Fibrillary Acidic Protein-Positive Cells Generate Neurons after Perinatal Hypoxic Injury
Bi B, Salmaso N, Komitova M, Simonini MV, Silbereis J, Cheng E, Kim J, Luft S, Ment LR, Horvath TL, Schwartz ML, Vaccarino FM. Cortical Glial Fibrillary Acidic Protein-Positive Cells Generate Neurons after Perinatal Hypoxic Injury. Journal Of Neuroscience 2011, 31: 9205-9221. PMID: 21697371, PMCID: PMC3142780, DOI: 10.1523/jneurosci.0518-11.2011.Peer-Reviewed Original ResearchConceptsGlial fibrillary acidic protein-positive cellsCortical excitatory neuronsProtein-positive cellsPerinatal hypoxic injuryPostnatal hypoxiaGenetic fate mappingCortical astrogliaPremature childrenHypoxic injuryBrain injuryNew neuronsPreterm childrenNeurogenic nicheCognitive recoveryExcitatory neuronsGenerate neuronsNeuronal fateNeuronsHypoxiaCortical parenchymaInjuryParenchymaFate mappingCellsChildrenDifferential Acute and Chronic Effects of Leptin on Hypothalamic Astrocyte Morphology and Synaptic Protein Levels
García-Cáceres C, Fuente-Martín E, Burgos-Ramos E, Granado M, Frago LM, Barrios V, Horvath T, Argente J, Chowen JA. Differential Acute and Chronic Effects of Leptin on Hypothalamic Astrocyte Morphology and Synaptic Protein Levels. Endocrinology 2011, 152: 1809-1818. PMID: 21343257, PMCID: PMC3860256, DOI: 10.1210/en.2010-1252.Peer-Reviewed Original ResearchConceptsGlial fibrillary acidic proteinChronic leptin exposureSynaptic inputsAstrocyte morphologyLeptin exposureGFAP levelsGlial structural proteinsSynaptic protein densityChronic leptin administrationAcute leptin treatmentSynaptic protein levelsAdult male ratsCentral leptin resistanceFibrillary acidic proteinLevels 1 hPossible direct effectGlial ensheathingNeonatal overnutritionGlial activationLeptin levelsLeptin administrationHypothalamic neuronsLeptin resistanceLeptin treatmentMale rats
2010
An Oscillatory Switch in mTOR Kinase Activity Sets Regulatory T Cell Responsiveness
Procaccini C, De Rosa V, Galgani M, Abanni L, Calì G, Porcellini A, Carbone F, Fontana S, Horvath TL, La Cava A, Matarese G. An Oscillatory Switch in mTOR Kinase Activity Sets Regulatory T Cell Responsiveness. Immunity 2010, 33: 929-941. PMID: 21145759, PMCID: PMC3133602, DOI: 10.1016/j.immuni.2010.11.024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4 AntigensCell ProliferationCells, CulturedClonal AnergyDisease ProgressionEncephalomyelitis, Autoimmune, ExperimentalForkhead Transcription FactorsHumansInterleukin-2Interleukin-2 Receptor alpha SubunitLeptinMiceMice, Inbred C57BLSignal TransductionSirolimusT-Lymphocytes, RegulatoryTOR Serine-Threonine KinasesConceptsTreg cellsAnergic stateInterleukin-2Treg cell expansionRegulatory T cellsExogenous interleukin-2T cell responsivenessCell receptor stimulationImmune toleranceT cellsCell responsivenessReceptor stimulationMTOR activationEarly downregulationMammalian targetMTOR kinase activityRapamycin (mTOR) pathwayProliferative capabilityTransient inhibitionUnderlying mechanismElevated activityEnergy metabolismCellsResponsivenessCell expansion
2004
CPG2 A brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors
Cottrell JR, Borok E, Horvath TL, Nedivi E. CPG2 A brain- and synapse-specific protein that regulates the endocytosis of glutamate receptors. Neuron 2004, 44: 677-690. PMID: 15541315, PMCID: PMC3065105, DOI: 10.1016/j.neuron.2004.10.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBlotting, NorthernBlotting, WesternBrainCells, CulturedClathrin-Coated VesiclesEndocytosisHumansIn Situ HybridizationMicroscopy, ElectronMolecular Sequence DataNerve Tissue ProteinsNeuronal PlasticityNeuronsReceptors, AMPAReceptors, GlutamateReceptors, N-Methyl-D-AspartateReverse Transcriptase Polymerase Chain ReactionSynapsesConceptsGlutamate receptorsClathrin-coated vesiclesBrain-specific splice variantSynapse-specific proteinsExcitatory synapsesReceptor endocytosisSYNE-1 geneConstitutive internalizationEndocytic mechanismsSynaptic AMPA receptorsDendritic spine sizeMembrane transportSplice variantsSynaptic proteinsNMDA receptorsAMPA receptorsProteinPostsynaptic plasticityNeurotransmitter receptorsEndocytosisSynaptic strengthLong-term maintenanceReceptorsSpine sizeInternalization
2002
ER-X: A Novel, Plasma Membrane-Associated, Putative Estrogen Receptor That Is Regulated during Development and after Ischemic Brain Injury
Toran-Allerand CD, Guan X, MacLusky NJ, Horvath TL, Diano S, Singh M, Connolly ES, Nethrapalli S, Tinnikov AA. ER-X: A Novel, Plasma Membrane-Associated, Putative Estrogen Receptor That Is Regulated during Development and after Ischemic Brain Injury. Journal Of Neuroscience 2002, 22: 8391-8401. PMID: 12351713, PMCID: PMC6757764, DOI: 10.1523/jneurosci.22-19-08391.2002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding, CompetitiveBlotting, WesternBrain IschemiaCaveolaeCell MembraneCell-Free SystemCells, CulturedCholesterolEnzyme ActivationEstradiolGene Expression Regulation, DevelopmentalIonophoresMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesNeocortexNeuronsReceptors, EstrogenRNA, MessengerSignal TransductionSubcellular FractionsSubstrate SpecificityConceptsMAPK cascadePlasma membraneExtracellular signal-regulated kinases ERK1Neuronal differentiationPlasma membrane-associatedPlasma membrane-associated ERsProtein kinase isoformsCell-free systemMembrane-associated ERER alphaPutative ERKinases ERK1Cell divisionER betaSustained phosphorylationKinase isoformsERK activationMembrane-associatedGene-disrupted miceNovel mechanismEstrogen receptorUterine plasma membranesInhibitory regulatorIschemic stroke injuryIschemic brain injury