2024
Elucidating a new path of CSF transport in the CNS
Benveniste H, Thomas J. Elucidating a new path of CSF transport in the CNS. The Lancet Neurology 2024, 23: 553-554. PMID: 38760087, DOI: 10.1016/s1474-4422(24)00164-9.Peer-Reviewed Original ResearchVEGF-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 signalingComplementary and Inducible creERT2 Mouse Models for Functional Evaluation of Endothelial Cell Subtypes in the Bone Marrow
Poulos M, Ramalingam P, Winiarski A, Gutkin M, Katsnelson L, Carter C, Pibouin-Fragner L, Eichmann A, Thomas J, Miquerol L, Butler J. Complementary and Inducible creERT2 Mouse Models for Functional Evaluation of Endothelial Cell Subtypes in the Bone Marrow. Stem Cell Reviews And Reports 2024, 20: 1135-1149. PMID: 38438768, PMCID: PMC11087254, DOI: 10.1007/s12015-024-10703-9.Peer-Reviewed Original ResearchBone marrowEndothelial cellsMouse modelAdult bone marrowArteriole endothelial cellsAdult BMOff-target activityHematopoietic dysfunctionAdult marrowHematopoietic homeostasisEndothelial cell subtypesVascular subtypeCre-expressing lineEndothelial subtypesEndothelial-specificMouse linesHSC activationCell subtypesEC subtypesParacrine signalingPerivascular cellsModulate HSC activationMarrowSubtypesAdult endotheliumCompartmentalized ocular lymphatic system mediates eye–brain immunity
Yin X, Zhang S, Lee J, Dong H, Mourgkos G, Terwilliger G, Kraus A, Geraldo L, Poulet M, Fischer S, Zhou T, Mohammed F, Zhou J, Wang Y, Malloy S, Rohner N, Sharma L, Salinas I, Eichmann A, Thomas J, Saltzman W, Huttner A, Zeiss C, Ring A, Iwasaki A, Song E. Compartmentalized ocular lymphatic system mediates eye–brain immunity. Nature 2024, 628: 204-211. PMID: 38418880, PMCID: PMC10990932, DOI: 10.1038/s41586-024-07130-8.Peer-Reviewed Original ResearchResponse to herpes simplex virusCentral nervous systemImmune response to herpes simplex virusPosterior eyeImmune responseTherapeutic immune responsesOptic nerve sheathCervical lymph nodesAdeno-associated virusCNS diseaseDeep cervical lymph nodesHerpes simplex virusImmune protected miceCentral nervous system tissueLymphatic drainage systemImmunological featuresAnatomical extensionNerve sheathOptic nerveGene therapyLymph nodesMultiple dosesSimplex virusLymphatic circuitLymphatic signal
2023
Editorial Expression of Concern: The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system
Lu X, le Noble F, Yuan L, Jiang Q, de Lafarge B, Sugiyama D, Bréant C, Claes F, De Smet F, Thomas J, Autiero M, Carmeliet P, Tessier-Lavigne M, Eichmann A. Editorial Expression of Concern: The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 2023, 625: e12-e12. PMID: 38110575, DOI: 10.1038/s41586-023-06944-2.Peer-Reviewed Original ResearchEXTH-59. IDENTIFICATION OF GROWTH HORMONE RECEPTOR AS A RELEVANT TARGET FOR PRECISION MEDICINE IN LOW-EGFR EXPRESSING GLIOBLASTOMA
Verreault M, Vilchis I, Rosenberg S, Lemaire N, Schmitt C, Guehennec J, Royer-Perron L, Thomas J, Lam T, Dingli F, Loew D, Ducray F, Paris S, Carpentier C, Marie Y, Laigle-Donadey F, Rousseau A, Pigat N, Boutillon F, Bielle F, Mokhtari K, Frank S, de Reynies A, Hoang-Xuan K, Sanson M, Goffin V, Idbaih A. EXTH-59. IDENTIFICATION OF GROWTH HORMONE RECEPTOR AS A RELEVANT TARGET FOR PRECISION MEDICINE IN LOW-EGFR EXPRESSING GLIOBLASTOMA. Neuro-Oncology 2023, 25: v237-v237. PMCID: PMC10639947, DOI: 10.1093/neuonc/noad179.0912.Peer-Reviewed Original ResearchGrowth hormone receptorOncogenic mechanismsCommon oncogenic mechanismThird of patientsDistinct molecular subsetsNew therapeutic approachesPromising therapeutic targetHuman GBM samplesPatient-derived cell linesLower eGFRMolecular subsetsExpression of proteinsGBM patientsTherapeutic approachesGlioblastoma patientsTherapeutic targetTumor growthGrowth hormoneEGFR overexpressionPharmacological inhibitionSOCS2 expressionTumor invasionPatientsHormone receptorsGBM samplesIntrathecal 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 systemConnexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone
Genet N, Genet G, Chavkin N, Paila U, Fang J, Vasavada H, Goldberg J, Acharya B, Bhatt N, Baker K, McDonnell S, Huba M, Sankaranarayanan D, Ma G, Eichmann A, Thomas J, Ffrench-Constant C, Hirschi K. Connexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone. Cell Reports 2023, 42: 112371. PMID: 37043357, PMCID: PMC10564973, DOI: 10.1016/j.celrep.2023.112371.Peer-Reviewed Original ResearchConceptsSubventricular zoneEndothelial cellsNSC proliferationNSC quiescenceAdult brain subventricular zoneBlood-brain barrierBrain subventricular zoneStem cell therapyNeural stem cell nicheNeurovascular interactionsNeuroblast generationAdult brainSingle-cell RNA sequencingNeurodegenerative disordersChannel-independent mannerCell therapySVZ-NSCsConnexin 43Expression of genesERK activationNSC regulationNSC behaviorRNA sequencingCx43Proliferation
2022
CSF-to-dura gateways
Thomas J, Benveniste H. CSF-to-dura gateways. Journal Of Experimental Medicine 2022, 220: e20221719. PMID: 36472584, PMCID: PMC9729850, DOI: 10.1084/jem.20221719.Peer-Reviewed Original ResearchTribute to Klaus Eichmann, Editor-in-Chief of Cellular and Molecular Life Sciences
Thomas J, Bruzzone R, El-Osta A, Claessens F, Ruysschaert J, Wilson D. Tribute to Klaus Eichmann, Editor-in-Chief of Cellular and Molecular Life Sciences. Cellular And Molecular Life Sciences 2022, 79: 529. PMID: 36166158, DOI: 10.1007/s00018-022-04532-7.Peer-Reviewed Original ResearchIdentification of growth hormone receptor as a relevant target for precision medicine in low‐EGFR expressing glioblastoma
Verreault M, Vilchis I, Rosenberg S, Lemaire N, Schmitt C, Guehennec J, Royer‐Perron L, Thomas J, Lam TT, Dingli F, Loew D, Ducray F, Paris S, Carpentier C, Marie Y, Laigle‐Donadey F, Rousseau A, Pigat N, Boutillon F, Bielle F, Mokhtari K, Frank SJ, de Reyniès A, Hoang‐Xuan K, Sanson M, Goffin V, Idbaih A. Identification of growth hormone receptor as a relevant target for precision medicine in low‐EGFR expressing glioblastoma. Clinical And Translational Medicine 2022, 12: e939. PMID: 35808822, PMCID: PMC9270581, DOI: 10.1002/ctm2.939.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorGrowth hormone receptorPatient-derived cell linesOncogenic mechanismsGene expression profilesCell linesGain of functionHormone receptorsExpression of proteinsCellular movementGrowth factor receptorHuman GBM samplesExpression profilesCell migrationCommon oncogenic mechanismThird of patientsDistinct molecular subsetsGBM samplesPromoter hypermethylationNew therapeutic approachesFactor receptorCell proliferationPharmacological inhibitionRelevant targetsOverexpressionConserved 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 1Publisher Correction: VEGF-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. Publisher Correction: VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours. Nature 2021, 590: e34-e34. PMID: 33500588, DOI: 10.1038/s41586-021-03204-z.Peer-Reviewed Original ResearchNeuroinvasion 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 ResearchThree-Dimensional Imaging of the Vertebral Lymphatic Vasculature and Drainage using iDISCO+ and Light Sheet Fluorescence Microscopy.
Jacob L, Brito J, Thomas JL. Three-Dimensional Imaging of the Vertebral Lymphatic Vasculature and Drainage using iDISCO+ and Light Sheet Fluorescence Microscopy. Journal Of Visualized Experiments 2020 PMID: 32510513, DOI: 10.3791/61099.Peer-Reviewed Original ResearchConceptsLight sheet fluorescence microscopySheet fluorescence microscopyLymphatic vasculatureFluorescence microscopyCentral nervous systemLymphatic vesselsBiologyLymphatic systemLymphatic networkJoint biologyWhole-mount preparationsUnprecedented opportunityImmune surveillanceNervous systemImmune cellsTissueMount preparationsVertebral columnCNS tissueCellsMagnaMacromoleculesWhole-Genome and RNA Sequencing Reveal Variation and Transcriptomic Coordination in the Developing Human Prefrontal Cortex
Werling DM, Pochareddy S, Choi J, An JY, Sheppard B, Peng M, Li Z, Dastmalchi C, Santpere G, Sousa AMM, Tebbenkamp ATN, Kaur N, Gulden FO, Breen MS, Liang L, Gilson MC, Zhao X, Dong S, Klei L, Cicek AE, Buxbaum JD, Adle-Biassette H, Thomas JL, Aldinger KA, O’Day D, Glass IA, Zaitlen NA, Talkowski ME, Roeder K, State MW, Devlin B, Sanders SJ, Sestan N. Whole-Genome and RNA Sequencing Reveal Variation and Transcriptomic Coordination in the Developing Human Prefrontal Cortex. Cell Reports 2020, 31: 107489. PMID: 32268104, PMCID: PMC7295160, DOI: 10.1016/j.celrep.2020.03.053.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBrainComputational BiologyDatabases, GeneticExome SequencingGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyGenomicsHumansPhenotypePolymorphism, Single NucleotidePrefrontal CortexQuantitative Trait LociSequence Analysis, RNATranscriptomeWhole Genome SequencingConceptsExpression levelsGene expression levelsTranscriptomic coordinationDisorder lociNeuropsychiatric traitsSpecific genesRisk lociGene expressionGenomic variantsDevelopmental stagesCell typesGenesLociTissue RNACommon variantsPostnatal stagesUnique resourceSpecific variantsExpressionEQTLsVariantsGenomeHuman prefrontal cortexRNATraits