2024
Meningeal lymphatic vessel dysfunction driven by CGRP signaling causes migraine-like pain in mice
Thomas J, Schindler E, Gottschalk C. Meningeal lymphatic vessel dysfunction driven by CGRP signaling causes migraine-like pain in mice. Journal Of Clinical Investigation 2024, 134: e182556. PMID: 39087472, PMCID: PMC11290958, DOI: 10.1172/jci182556.Peer-Reviewed Original ResearchConceptsBlocking CGRP signalingCGRP receptor componentsMigraine-like painCervical lymph nodesGap junction proteinPrimary headache disordersLymphatic vessel dysfunctionAcute migrainePharmacological blockadeLymph nodesHeadache disordersNeurological symptomsJunction proteinsCGRPLymphatic vesselsMeningeal lymphatic vesselsInducible knockoutVessel dysfunctionMigraineReceptor componentsHeadachePainPathophysiologyDysfunctionMiceVEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model
Boisserand L, Geraldo L, Bouchart J, Kamouh M, Lee S, Sanganahalli B, Spajer M, Zhang S, Lee S, Parent M, Xue Y, Skarica M, Yin X, Guegan J, Boyé K, Leser F, Jacob L, Poulet M, Li M, Liu X, Velazquez S, Singhabahu R, Robinson M, Askenase M, Osherov A, Sestan N, Zhou J, Alitalo K, Song E, Eichmann A, Sansing L, Benveniste H, Hyder F, Thomas J. VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model. Journal Of Experimental Medicine 2024, 221: e20221983. PMID: 38442272, PMCID: PMC10913814, DOI: 10.1084/jem.20221983.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factor-CDeep cervical lymph nodesCentral nervous systemEffect of vascular endothelial growth factor-CMeningeal lymphatic vesselsAmeliorated motor performanceCervical lymph nodesIschemic strokeVEGF-C overexpressionIncreased BDNF signalingAcute ischemic strokeBrain cellsIncreased CSF drainageIschemic stroke outcomesModel of ischemic strokeMouse model of ischemic strokeImmune surveillanceCSF drainageLymph nodesFluid drainageNucleus RNA sequencingLymphatic growthLymphatic drainageMouse modelBDNF signaling
2023
Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma
Khang M, Lee J, Lee T, Suh H, Lee S, Cavaliere A, Rushing A, Geraldo L, Belitzky E, Rossano S, de Feyter H, Shin K, Huttner A, Roussel M, Thomas J, Carson R, Marquez-Nostra B, Bindra R, Saltzman W. Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma. Science Translational Medicine 2023, 15: eadi1617. PMID: 37910601, PMCID: PMC11078331, DOI: 10.1126/scitranslmed.adi1617.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidDelivery of drugsEffective therapyTherapeutic indexPARP inhibitorsBlood-brain barrierSite of tumorRapid systemic clearanceXenograft mouse modelSolvent evaporation processAdministration of substancesLeptomeningeal spreadIntrathecal deliveryLeptomeningeal metastasesBrain penetrationSystemic clearanceTumor regressionPolymer nanoparticlesMetastatic medulloblastomaMouse modelPediatric medulloblastomaDrug accumulationCSF turnoverEncapsulated drugsPET imagingCCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma
Geraldo L, Garcia C, Xu Y, Leser F, Grimaldi I, de Camargo Magalhães E, Dejaegher J, Solie L, Pereira C, Correia A, De Vleeschouwer S, Tavitian B, Canedo N, Mathivet T, Thomas J, Eichmann A, Lima F. CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma. Cellular And Molecular Life Sciences 2023, 80: 179. PMID: 37314567, PMCID: PMC10267017, DOI: 10.1007/s00018-023-04788-7.Peer-Reviewed Original ResearchConceptsMicroglia/macrophage recruitmentC chemokine receptor type 7CCL21-CCR7Central nervous systemMacrophage recruitmentTumor microenvironmentChemokine receptor type 7Fatal primary tumorMouse GBM modelsChemokine ligand 21Potential therapeutic targetVEGF-A productionTumor cell deathCCR7 expressionTherapeutic optionsPrimary tumorPoor survivalCurrent treatmentGBM patientsTumor cell migrationTherapeutic targetBrain cancerNervous systemChemotherapy resistanceLigand 21Three-dimensional imaging of vascular development in the mouse epididymis.
Damon-Soubeyrand C, Bongiovanni A, Chorfa A, Goubely C, Pirot N, Pardanaud L, Piboin-Fragner L, Vachias C, Bravard S, Guiton R, Thomas J, Saez F, Kocer A, Tardivel M, Drevet J, Henry-Berger J. Three-dimensional imaging of vascular development in the mouse epididymis. ELife 2023, 12 PMID: 37310207, PMCID: PMC10264076, DOI: 10.7554/elife.82748.Peer-Reviewed Original ResearchConceptsProtection of spermatozoaComplex immune functionsAccessory tubulesVascular developmentMouse epididymisCellular levelSecretory roleImportant playersMale fertilityMale reproductive systemOrgan clearingMature adult miceReproductive systemTransgenic mouse modelFunctional maturationPeripheral toleranceBlood markersImmune responseLymphatic networkImmune functionKey determinantMouse modelSurvival of spermatozoaAdult miceImmune system
2022
Conserved meningeal lymphatic drainage circuits in mice and humans
Jacob L, de Brito Neto J, Lenck S, Corcy C, Benbelkacem F, Geraldo LH, Xu Y, Thomas JM, Kamouh M, Spajer M, Potier MC, Haik S, Kalamarides M, Stankoff B, Lehericy S, Eichmann A, Thomas JL. Conserved meningeal lymphatic drainage circuits in mice and humans. Journal Of Experimental Medicine 2022, 219: e20220035. PMID: 35776089, PMCID: PMC9253621, DOI: 10.1084/jem.20220035.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidVessel wall magnetic resonance imagingDural venous sinusesMagnetic resonance imagingCavernous sinusSystemic injectionImmune surveillanceVenous sinusesGlymphatic systemNeurological diseasesDura materVW-MRIResonance imagingBrain tissueEmissary veinsNeurological pathologiesAnterior partCSF outflowTracer injectionDrainage circuitThree-dimensional anatomyLymphatic vesselsPatientsDiagnostic toolSinus
2021
SLIT2/ROBO signaling in tumor-associated microglia/macrophages drives glioblastoma immunosuppression and vascular dysmorphia
Geraldo LH, Xu Y, Jacob L, Pibouin-Fragner L, Rao R, Maïssa N, Verreault M, Lemaire N, Knosp C, Lesaffre C, Daubon T, Dejaegher J, Solie L, Rudewicz J, Viel T, Tavitian B, De Vleeschouwer S, Sanson M, Bikfalvi A, Idbaih A, Lu QR, Lima F, Thomas. JL, Eichmann A, Mathivet T. SLIT2/ROBO signaling in tumor-associated microglia/macrophages drives glioblastoma immunosuppression and vascular dysmorphia. Journal Of Clinical Investigation 2021, 131 PMID: 34181595, PMCID: PMC8363292, DOI: 10.1172/jci141083.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsDisease ProgressionGene Expression Regulation, NeoplasticGene Knockdown TechniquesGlioblastomaHeterograftsHumansImmune ToleranceIntercellular Signaling Peptides and ProteinsMacrophagesMiceMice, Inbred C57BLMicrogliaNerve Tissue ProteinsPrognosisReceptors, ImmunologicSignal TransductionTumor MicroenvironmentConceptsSLIT2/ROBOTumor growthPatient-derived GBM xenograftsTumor microenvironmentKnockdown of SLIT2Tumor vessel functionMouse glioma cellsImmunotherapeutic targetPoor survivalGBM xenograftsBrain tumorsGBM microenvironmentMacrophage invasionSLIT2 expressionMalignant progressionVessel functionMacrophage chemotaxisGlioma cellsEnhanced efficacySLIT2Migration of cellsImmunosuppressionImmunotherapyGene expression profilesRoundabout 1Neuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2020
Les vaisseaux lymphatiques méningés, une cible potentielle pour le traitement des tumeurs cérébrales
Thomas JL, Song E, Boisserand L, Iwasaki A. Les vaisseaux lymphatiques méningés, une cible potentielle pour le traitement des tumeurs cérébrales. Médecine/sciences 2020, 36: 709-713. PMID: 32821046, PMCID: PMC8158397, DOI: 10.1051/medsci/2020141.Peer-Reviewed Original ResearchVEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours
Song E, Mao T, Dong H, Boisserand LSB, Antila S, Bosenberg M, Alitalo K, Thomas JL, Iwasaki A. VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours. Nature 2020, 577: 689-694. PMID: 31942068, PMCID: PMC7100608, DOI: 10.1038/s41586-019-1912-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCD8-Positive T-LymphocytesCell Cycle CheckpointsCell Line, TumorCell MovementCentral Nervous SystemCross-PrimingFemaleGlioblastomaHEK293 CellsHumansImmunologic MemoryImmunologic SurveillanceLymph NodesLymphangiogenesisLymphatic VesselsMaleMelanomaMeningesMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorVascular Endothelial Growth Factor CConceptsCD8 T cellsCentral nervous systemT cellsImmune responseBrain tumorsImmune surveillanceLymphatic drainageNervous systemAntigen-specific immune responsesDeep cervical lymph nodesCapacity of VEGFCervical lymph nodesCheckpoint blockade therapyMeningeal lymphatic systemVascular endothelial growth factor CNew therapeutic approachesUncontrolled tumor growthMeningeal lymphatic vasculatureBlockade therapyLymph nodesTherapeutic approachesMouse modelTumor growthMemory responsesTumors
2019
Minimally Invasive Delivery of Microbeads with Encapsulated, Viable and Quiescent Neural Stem Cells to the Adult Subventricular Zone
Matta R, Lee S, Genet N, Hirschi KK, Thomas JL, Gonzalez AL. Minimally Invasive Delivery of Microbeads with Encapsulated, Viable and Quiescent Neural Stem Cells to the Adult Subventricular Zone. Scientific Reports 2019, 9: 17798. PMID: 31780709, PMCID: PMC6882840, DOI: 10.1038/s41598-019-54167-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell EncapsulationCell LineCell ProliferationCell SurvivalEndothelial CellsLateral VentriclesMaleMatrix MetalloproteinasesMiceMice, Inbred C57BLMicrospheresNeural Stem CellsNeuronsPolyethylene GlycolsRecovery of FunctionStem Cell NicheStem Cell TransplantationConceptsEndothelial cellsSubventricular zoneNSC quiescenceNon-injury modelQuiescent neural stem cellsAdult subventricular zoneNeuronal stem cellsStem cellsNeural stem cellsFunctional recoveryNeurological injuryInflammatory responseNeural stem cell maintenanceNSC deliveryNeural tissue repairNeurological diseasesMouse brainCell therapyNSC viabilityBrainTissue repairInjuryCo-encapsulated cellsSurvivalDeliveryEndophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis
Genet G, Boyé K, Mathivet T, Ola R, Zhang F, Dubrac A, Li J, Genet N, Henrique Geraldo L, Benedetti L, Künzel S, Pibouin-Fragner L, Thomas JL, Eichmann A. Endophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis. Nature Communications 2019, 10: 2350. PMID: 31138815, PMCID: PMC6538628, DOI: 10.1038/s41467-019-10359-x.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAnimalsCell MovementCell PolarityCell ProliferationCell SurvivalEndocytosisEndothelial CellsIntercellular Signaling Peptides and ProteinsMAP Kinase Signaling SystemMiceMice, KnockoutNeovascularization, PhysiologicNerve Tissue ProteinsP21-Activated KinasesReceptors, ImmunologicRetinal VesselsVascular Endothelial Growth Factor Receptor-2ConceptsEndophilin A2Endothelial cell migrationSprouting angiogenesisCell migrationFront-rear polarityBAR domain proteinsFront-rear polarizationClathrin-independent internalizationSpecific endocytic pathwaysVEGFR2 endocytosisEndocytic pathwayAngiogenesis defectsEffector PAKTip cellsSlit-RoboActivation of VEGFR2Downstream activationVEGFR2 internalizationCell behaviorPathological angiogenesisCritical mediatorEndocytosisPathological conditionsRNA Profiling of the Human and Mouse Spinal Cord Stem Cell Niches Reveals an Embryonic-like Regionalization with MSX1+ Roof-Plate-Derived Cells
Ghazale H, Ripoll C, Leventoux N, Jacob L, Azar S, Mamaeva D, Glasson Y, Calvo CF, Thomas JL, Meneceur S, Lallemand Y, Rigau V, Perrin FE, Noristani HN, Rocamonde B, Huillard E, Bauchet L, Hugnot JP. RNA Profiling of the Human and Mouse Spinal Cord Stem Cell Niches Reveals an Embryonic-like Regionalization with MSX1+ Roof-Plate-Derived Cells. Stem Cell Reports 2019, 12: 1159-1177. PMID: 31031189, PMCID: PMC6524006, DOI: 10.1016/j.stemcr.2019.04.001.Peer-Reviewed Original ResearchConceptsTranscription factorsRNA profilingDevelopmental transcription factorsDorsal-ventral patternStem cell nicheEpendymal zoneMolecular resourcesMammalian lesionsConserved expressionCell nicheNeural stem cellsCell diversityPossible endogenous sourceQuiescent cellsGenesFloor plateStem cellsMsx1Endogenous sourcesTransgenic miceCellsProfilingSpinal cordCentral canalExpression
2018
Oligodendrocyte precursor survival and differentiation requires chromatin remodeling by Chd7 and Chd8
Marie C, Clavairoly A, Frah M, Hmidan H, Yan J, Zhao C, Van Steenwinckel J, Daveau R, Zalc B, Hassan B, Thomas JL, Gressens P, Ravassard P, Moszer I, Martin DM, Lu QR, Parras C. Oligodendrocyte precursor survival and differentiation requires chromatin remodeling by Chd7 and Chd8. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e8246-e8255. PMID: 30108144, PMCID: PMC6126750, DOI: 10.1073/pnas.1802620115.Peer-Reviewed Original ResearchConceptsChromatin remodelersProliferation-differentiation balanceNormal developmentChromatin accessibility analysisOligodendrocyte precursor cellsChromatin closingChromatin remodelingChromatin openingTranscriptional repressionGenetic interactionsUncharacterized functionGenetic reprogrammingRisk-associated genesTranscriptional activationKey regulatorNeurodevelopmental defectsPrecursor survivalLineage cellsCHD7RemodelersOligodendrocyte lineage cellsPrecursor cellsGlioma formationBinding profileCHD8The phenotypic and functional properties of mouse yolk-sac-derived embryonic macrophages
Yosef N, Vadakkan TJ, Park JH, Poché RA, Thomas JL, Dickinson ME. The phenotypic and functional properties of mouse yolk-sac-derived embryonic macrophages. Developmental Biology 2018, 442: 138-154. PMID: 30016639, PMCID: PMC6190604, DOI: 10.1016/j.ydbio.2018.07.009.Peer-Reviewed Original ResearchConceptsEmbryonic macrophagesErythro-myeloid progenitorsNeural stem/progenitor cellsExtra-embryonic yolk sacMouse neural stem/progenitor cellsEndothelial cell cord formationStem/progenitor cellsNon-immune functionsEC tube formationDevelopmental processesPrimitive erythroblastsTissue-resident populationsCord formationEarly cellsDirect cellKey inducerProgenitor cellsYolk sacCell contactEssential roleTube formationSpecialized propertiesBone marrowCell maturationProgenitors
2017
Modulation of Endothelial Bone Morphogenetic Protein Receptor Type 2 Activity by Vascular Endothelial Growth Factor Receptor 3 in Pulmonary Arterial Hypertension
Hwangbo C, Lee HW, Kang H, Ju H, Wiley DS, Papangeli I, Han J, Kim JD, Dunworth WP, Hu X, Lee S, El-Hely O, Sofer A, Pak B, Peterson L, Comhair S, Hwang EM, Park JY, Thomas J, Bautch VL, Erzurum SC, Chun HJ, Jin SW. Modulation of Endothelial Bone Morphogenetic Protein Receptor Type 2 Activity by Vascular Endothelial Growth Factor Receptor 3 in Pulmonary Arterial Hypertension. Circulation 2017, 135: 2288-2298. PMID: 28356442, PMCID: PMC5523010, DOI: 10.1161/circulationaha.116.025390.Peer-Reviewed Original ResearchConceptsBMP receptor type 2Vascular endothelial growth factor receptor 3Growth factor receptor 3Zebrafish embryosPulmonary arterial endothelial cellsArterial endothelial cellsVEGFR3 expressionBone morphogenetic protein (BMP) signalingPulmonary arterial hypertensionMorphogenetic protein signalingEndothelial cellsFamilial pulmonary arterial hypertensionBMPR2 functionsPrimary lung endothelial cellsImpaired BMPBMP signalingBMP stimulationProtein signalingReceptor 3Endothelial-specific deletionEctopic angiogenesisKey regulatorHuman endothelial cellsArterial hypertensionLung endothelial cells
2016
Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging
Han L, Kong DK, Zheng MQ, Murikinati S, Ma C, Yuan P, Li L, Tian D, Cai Q, Ye C, Holden D, Park JH, Gao X, Thomas JL, Grutzendler J, Carson RE, Huang Y, Piepmeier JM, Zhou J. Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging. ACS Nano 2016, 10: 4209-4218. PMID: 26967254, PMCID: PMC5257033, DOI: 10.1021/acsnano.5b07573.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBiological TransportBlood-Brain BarrierBrain NeoplasmsCell Line, TumorDecanoic AcidsDrug Delivery SystemsEthanolaminesFemaleGenetic TherapyHeterograftsHumansMatrix Metalloproteinase 2MiceMice, Inbred C57BLNanoparticlesOptical ImagingPaclitaxelPermeabilityPolymersPurinesPyrazolesScorpion VenomsTranscytosisTumor MicroenvironmentConceptsBlood-brain barrierLow delivery efficiencyTransport of nanoparticlesCancer gene therapyNanoparticle deliveryMore nanoparticlesBrain tumorsNanoparticlesDelivery efficiencyGene therapySystemic deliveryNPsBrain malignanciesBBB modulatorsPharmacological agentsBrain cancerBrain regionsTumorsDeliveryBrainImproved treatmentInadequate amountsPositive feedback loopChemotherapyMalignancy
2015
Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization
Dubrac A, Genet G, Ola R, Zhang F, Pibouin-Fragner L, Han J, Zhang J, Thomas JL, Chedotal A, Schwartz MA, Eichmann A. Targeting NCK-Mediated Endothelial Cell Front-Rear Polarity Inhibits Neovascularization. Circulation 2015, 133: 409-421. PMID: 26659946, PMCID: PMC4729599, DOI: 10.1161/circulationaha.115.017537.Peer-Reviewed Original ResearchConceptsFront-rear polaritySprouting angiogenesisSignal integration mechanismImportant drug targetsNck adaptorsCytoskeletal dynamicsEndothelial cell migrationEmbryonic developmentAngiogenesis defectsPAK2 activationVessel sproutsNumber of diseasesBlood vessel growthDrug targetsCell migrationPostnatal retinaAngiogenic growthNckNck1AdaptorVessel growthKey processesEndothelial cellsPathological ocular neovascularizationInhibits neovascularizationVascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis
Poulos MG, Crowley MJP, Gutkin MC, Ramalingam P, Schachterle W, Thomas JL, Elemento O, Butler JM. Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis. Stem Cell Reports 2015, 5: 881-894. PMID: 26441307, PMCID: PMC4649106, DOI: 10.1016/j.stemcr.2015.08.018.Peer-Reviewed Original ResearchConceptsBM endothelial cellsHematopoietic stem cellsBone marrowDevelopment of therapiesAdult bone marrowCytokine profileMyeloablative regimensMyeloablative irradiationStem cell factorRegenerative hematopoiesisPerivascular cellsCellular therapyEndothelial cellsDisease statesCytokine supplementationVascular platformCell factorVascular nicheTherapyPrevious reportsStem cellsEmbryonic Stem Cells License a High Level of Dormant Origins to Protect the Genome against Replication Stress
Ge XQ, Han J, Cheng EC, Yamaguchi S, Shima N, Thomas JL, Lin H. Embryonic Stem Cells License a High Level of Dormant Origins to Protect the Genome against Replication Stress. Stem Cell Reports 2015, 5: 185-194. PMID: 26190528, PMCID: PMC4618655, DOI: 10.1016/j.stemcr.2015.06.002.Peer-Reviewed Original ResearchConceptsEmbryonic stem cellsStem/progenitor cellsNeural stem/progenitor cellsStem cellsProgenitor cellsTissue stem/progenitor cellsMCM2-7 complexDNA replication originsTissue-specific stem/progenitor cellsStem cell typesGenome integrityGenomic integrityReplication stressDormant originsReplication forksReplicative stressDNA replicationReplication originsNeural lineagesDNA damageS phaseCell typesAbnormal neurogenesisCellsGenome