Featured Publications
Short-term consumption of highly processed diets varying in macronutrient content impair the sense of smell and brain metabolism in mice
Makhlouf M, Souza D, Kurian S, Bellaver B, Ellis H, Kuboki A, Al-Naama A, Hasnah R, Venturin G, da Costa J, Venugopal N, Manoel D, Mennella J, Reisert J, Tordoff M, Zimmer E, Saraiva L. Short-term consumption of highly processed diets varying in macronutrient content impair the sense of smell and brain metabolism in mice. Molecular Metabolism 2023, 79: 101837. PMID: 37977411, PMCID: PMC10724696, DOI: 10.1016/j.molmet.2023.101837.Peer-Reviewed Original ResearchConceptsMacronutrient contentIncrease food safetyGrain-based dietShort-term consumptionElectro-olfactogramFood safetyProcessed dietsFood processingBrain regionsBrain metabolismOdor-guided behaviorStandard chow dietShort-term intakeDietGlucose metabolism imagingHigh-fat dietFoodResponses to odorantsBrain glucose metabolismOlfactory mucosaModern dietFood consumptionChow dietChronic consumptionMetabolic phenotypeA 3D transcriptomics atlas of the mouse nose sheds light on the anatomical logic of smell
Ruiz Tejada Segura M, Abou Moussa E, Garabello E, Nakahara T, Makhlouf M, Mathew L, Wang L, Valle F, Huang S, Mainland J, Caselle M, Osella M, Lorenz S, Reisert J, Logan D, Malnic B, Scialdone A, Saraiva L. A 3D transcriptomics atlas of the mouse nose sheds light on the anatomical logic of smell. Cell Reports 2022, 38: 110547. PMID: 35320714, PMCID: PMC8995392, DOI: 10.1016/j.celrep.2022.110547.Peer-Reviewed Original ResearchCongenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease
Kubo S, Fritz J, Raquer-McKay H, Kataria R, Vujkovic-Cvijin I, Al-Shaibi A, Yao Y, Zheng L, Zou J, Waldman A, Jing X, Farley T, Park A, Oler A, Charles A, Makhlouf M, AbouMoussa E, Hasnah R, Saraiva L, Ganesan S, Al-Subaiey A, Matthews H, Flano E, Lee H, Freeman A, Sefer A, Sayar E, Çakır E, Karakoc-Aydiner E, Baris S, Belkaid Y, Ozen A, Lo B, Lenardo M. Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease. Nature Immunology 2021, 23: 75-85. PMID: 34937930, PMCID: PMC11060421, DOI: 10.1038/s41590-021-01093-y.Peer-Reviewed Original ResearchMeSH KeywordsA549 CellsADAM17 ProteinAnimalsCarrier ProteinsChildChild, PreschoolCitrobacter rodentiumColitisCytokinesEnterobacteriaceae InfectionsFemaleHEK293 CellsHumansInfant, NewbornMacrophagesMaleMiceMice, Inbred C57BLMutationPrimary Immunodeficiency DiseasesPseudomonas aeruginosaPseudomonas InfectionsSignal TransductionConceptsIRhom2 deficiencyLoss-of-function mutationsLocal microbial environmentLoss of iRhom2Diverse clinical phenotypesRecurrent respiratory infectionsWild-type miceRelease of cytokinesTumor necrosis factorHemorrhagic colitisCitrobacter rodentiumADAM17 metalloproteinaseFecal microbiotaSuperfamily membersRecurrent infectionsRecurrent pneumoniaTumor necrosisLung involvementColonic involvementHuman immunodeficiencyInflammatory colitisMicrobial environmentOral speciesPseudomonas aeruginosaColitis patientsDeconstructing the mouse olfactory percept through an ethological atlas
Manoel D, Makhlouf M, Arayata C, Sathappan A, Da'as S, Abdelrahman D, Selvaraj S, Hasnah R, Mainland J, Gerkin R, Saraiva L. Deconstructing the mouse olfactory percept through an ethological atlas. Current Biology 2021, 31: 2809-2818.e3. PMID: 33957076, PMCID: PMC8282700, DOI: 10.1016/j.cub.2021.04.020.Peer-Reviewed Original ResearchConceptsOlfactory perceptionMouse behaviorStudy of olfactory perceptionOdor perceptionBehavioral responsesPhysicochemical properties of odorantsHuman odor perceptionProperties of odorantsOdor identityOlfactory behaviorTarget odorOdorOdor concentrationPerceptionMiceBehaviorNon-humanResponseMultiple concentrationsDifferential regulation of the immune system in a brain-liver-fats organ network during short-term fasting
Huang S, Makhlouf M, AbouMoussa E, Segura M, Mathew L, Wang K, Leung M, Chaussabel D, Logan D, Scialdone A, Garand M, Saraiva L. Differential regulation of the immune system in a brain-liver-fats organ network during short-term fasting. Molecular Metabolism 2020, 40: 101038. PMID: 32526449, PMCID: PMC7339127, DOI: 10.1016/j.molmet.2020.101038.Peer-Reviewed Original ResearchConceptsShort-term fastingGene Ontology enrichment analysisOntology enrichment analysisReactome pathway analysisInnate immune signalingCombination of multivariate analysisImmune systemPriming of adaptive immunityChronic immunological disordersTranscriptional dynamicsGene setsGene OntologyWhite adipose tissueAdipose tissueProtein dataRNA sequencingBrown adipose tissueExpression analysisEnrichment analysisImmune signalingProfiles of miceDifferential regulationBiological pathwaysPathway analysisMolecular mechanismsAdipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration
Ambrosi T, Scialdone A, Graja A, Gohlke S, Jank A, Bocian C, Woelk L, Fan H, Logan D, Schürmann A, Saraiva L, Schulz T. Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration. Cell Stem Cell 2017, 20: 771-784.e6. PMID: 28330582, PMCID: PMC5459794, DOI: 10.1016/j.stem.2017.02.009.Peer-Reviewed Original ResearchConceptsStem cell-basedHematopoietic regenerationAdipocyte accumulationStem cell-like characteristicsCell-like characteristicsBone resident cellsDipeptidyl peptidase-4Bone marrow cavityCompetitive repopulationLethal irradiationHematopoietic nicheBone marrowCell-basedPeptidase-4Osteogenic lineageAged animalsBone healingDiabetes therapyAdipocyte lineageBoneMarrow cavityAge-dependentMolecular identityObesityAdipogenic lineagesCombinatorial effects of odorants on mouse behavior
Saraiva L, Kondoh K, Ye X, Yoon K, Hernandez M, Buck L. Combinatorial effects of odorants on mouse behavior. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e3300-e3306. PMID: 27208093, PMCID: PMC4988607, DOI: 10.1073/pnas.1605973113.Peer-Reviewed Original ResearchConceptsTrace amine-associated receptorsOdor aversionBehavioral effectsInstinctive behavioral responsesBinary odor mixturesEffects of odorsOdorant receptorsAversive responsesPredator odorMouse behaviorOdor stimuliOdor mixturesOdor responsesOdor perceptionReceptor antagonismBehavioral responsesOdor detectionSingle receptorSensory inputInstinctive behaviorAversionOdorStereotyped natureReceptor inputMouse noseHierarchical deconstruction of mouse olfactory sensory neurons: from whole mucosa to single-cell RNA-seq
Saraiva L, Ibarra-Soria X, Khan M, Omura M, Scialdone A, Mombaerts P, Marioni J, Logan D. Hierarchical deconstruction of mouse olfactory sensory neurons: from whole mucosa to single-cell RNA-seq. Scientific Reports 2015, 5: 18178. PMID: 26670777, PMCID: PMC4680959, DOI: 10.1038/srep18178.Peer-Reviewed Original ResearchConceptsMature olfactory sensory neuronsOlfactory sensory neuronsRNA-seqOR genesGene expressionSingle-cell RNA-seqIntact OR genesOlfactory receptorsCell typesSingle-nucleotide polymorphismsOR-expressing OSNsOR gene expressionIntact olfactory receptorsNeuron-one receptor ruleCrude tissue samplesMonoallelic expressionNeuronal cell typesMouse olfactory mucosaMultiple cell typesChemosensory tissuesGenesCellular heterogeneityOlfactory mucosaSensory neuronsNon-neuronalA Large-Scale Analysis of Odor Coding in the Olfactory Epithelium
Nara K, Saraiva L, Ye X, Buck L. A Large-Scale Analysis of Odor Coding in the Olfactory Epithelium. Journal Of Neuroscience 2011, 31: 9179-9191. PMID: 21697369, PMCID: PMC3758579, DOI: 10.1523/jneurosci.1282-11.2011.Peer-Reviewed Original ResearchConceptsOlfactory sensory neuronsOdor qualityOdor recognitionMouse olfactory sensory neuronsOdorant receptorsEncode odor identityExpressed odorant receptorOdor identityOdor codingOlfactory epitheliumSensory neuronsPerceived odorMultiple odorantsSensory inputInnate behaviorsOdorLarge-scale analysisOR genesMiceCombinatorial code
2024
Caloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice
Rinne C, Soultoukis G, Oveisi M, Leer M, Schmidt-Bleek O, Burkhardt L, Bucher C, Moussa E, Makhlouf M, Duda G, Saraiva L, Schmidt-Bleek K, Schulz T. Caloric restriction reduces trabecular bone loss during aging and improves bone marrow adipocyte endocrine function in male mice. Frontiers In Endocrinology 2024, 15: 1394263. PMID: 38904042, PMCID: PMC11188307, DOI: 10.3389/fendo.2024.1394263.Peer-Reviewed Original ResearchConceptsBone marrow adipose tissueTrabecular bone lossAged miceCaloric restrictionBone lossEndocrine profileMale C57BL6J miceCardio-metabolic diseasesTime of CRAge-matched littermatesBiochemical lipid profilesAssess bone microstructureFree food accessC57BL6J miceBone healthYoung miceContext of agingMale miceDietary interventionNutritional interventionAnatomical localizationLipid profileAdipogenic gene expressionBone dysfunctionTrabecular bone structure
2023
Genome-Wide RNA Tomography in the Mouse Whole Olfactory Mucosa
Moussa E, Makhlouf M, Mathew L, Saraiva L. Genome-Wide RNA Tomography in the Mouse Whole Olfactory Mucosa. Methods In Molecular Biology 2023, 2710: 19-30. PMID: 37688721, DOI: 10.1007/978-1-0716-3425-7_2.Peer-Reviewed Original Research
2022
The quality of energy- and macronutrient-balanced diets regulates host susceptibility to influenza in mice
Cootes T, Bhattacharyya N, Huang S, Daniel L, Bell-Anderson K, Stifter S, Chew T, Solon-Biet S, Saraiva L, Cai Y, Chen X, Simpson S, Feng C. The quality of energy- and macronutrient-balanced diets regulates host susceptibility to influenza in mice. Cell Reports 2022, 41: 111638. PMID: 36384123, DOI: 10.1016/j.celrep.2022.111638.Peer-Reviewed Original ResearchConceptsGrain-based chow dietOutcome of host-pathogen interactionsSusceptibility to influenzaHost resistance to infectionInterferon (IFN)-gHost-pathogen interactionsMortality to infectionDiet compositionInfluenza infectionResistance to infectionHost phenotypeChow dietInfection susceptibilityHost defenseImpact of diet compositionExtrinsic signalsMiceLaboratory rodent dietHeightened susceptibilityInfectionAdaptive homeostasisAIN93GRodent dietIndividual macronutrientsInfluenzaOdor blocking of stress hormone responses
Lee E, Saraiva L, Hanchate N, Ye X, Asher G, Ho J, Buck L. Odor blocking of stress hormone responses. Scientific Reports 2022, 12: 8773. PMID: 35610316, PMCID: PMC9130126, DOI: 10.1038/s41598-022-12663-x.Peer-Reviewed Original ResearchConceptsCorticotropin-releasing hormone neuronsBed nucleus of the stria terminalisOdor blockingHypothalamic corticotropin-releasing hormone neuronsInhibitory neuronsInhibition of excitatory neuronsBlood stress hormonesStress-induced increaseActivity of inhibitory neuronsActivate inhibitory neuronsHypothalamic ventromedial nucleusStress hormone responsesBed nucleusStria terminalisTransmit stress signalsPredator odorSocial confrontationVentromedial nucleusStress hormonesHormone neuronsAllay stressPhysical restraintExcitatory neuronsOdorHormonal responses
2018
Interspecific variation of olfactory preferences in flies, mice, and humans
Manoel D, Makhlouf M, Scialdone A, Saraiva L. Interspecific variation of olfactory preferences in flies, mice, and humans. Chemical Senses 2018, 44: 7-9. PMID: 30445540, PMCID: PMC6295792, DOI: 10.1093/chemse/bjy074.Peer-Reviewed Original Research
2017
Variation in olfactory neuron repertoires is genetically controlled and environmentally modulated
Ibarra-Soria X, Nakahara T, Lilue J, Jiang Y, Trimmer C, Souza M, Netto P, Ikegami K, Murphy N, Kusma M, Kirton A, Saraiva L, Keane T, Matsunami H, Mainland J, Papes F, Logan D. Variation in olfactory neuron repertoires is genetically controlled and environmentally modulated. ELife 2017, 6: e21476. PMID: 28438259, PMCID: PMC5404925, DOI: 10.7554/elife.21476.Peer-Reviewed Original ResearchConceptsOlfactory sensory neurons subtypesOlfactory sensory neuronsMouse olfactory sensory neuronsNeuronal diversityOlfactory receptorsOlfactory sensory systemTime-dependent mannerGenetically identical miceRNA sequencing-based methodsSub-stratifiedNeuronal repertoireSensory neuronsSubtype distributionIdentical miceOlfactory stimulationGenetic variationSubtypesMiceEnvironmental factorsDiversityReceptorsRepertoireSensory systemsNeuronsHeterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing
Lam B, Cimino I, Polex-Wolf J, Kohnke S, Rimmington D, Iyemere V, Heeley N, Cossetti C, Schulte R, Saraiva L, Logan D, Blouet C, O'Rahilly S, Coll A, Yeo G. Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing. Molecular Metabolism 2017, 6: 383-392. PMID: 28462073, PMCID: PMC5404100, DOI: 10.1016/j.molmet.2017.02.007.Peer-Reviewed Original ResearchConceptsPOMC neuronsArcuate POMC neuronsControl of body weightUnbiased clustering analysisExpressed low levelsExpressed high levelsArcuate proopiomelanocortinRNA sequencingLeptin receptorAtlas of gene expressionSingle cell RNA sequencingGene expression profilesSingle-cell RNA sequencingCell RNA sequencingNeuronsBody weightLeptinInsulin receptorProopiomelanocortinHeterogeneous populationReceptorsExpression profilesGene expressionExpression
2015
Computational assignment of cell-cycle stage from single-cell transcriptome data
Scialdone A, Natarajan K, Saraiva L, Proserpio V, Teichmann S, Stegle O, Marioni J, Buettner F. Computational assignment of cell-cycle stage from single-cell transcriptome data. Methods 2015, 85: 54-61. PMID: 26142758, DOI: 10.1016/j.ymeth.2015.06.021.Peer-Reviewed Original ResearchConceptsCell cycle stageTranscriptomes of single cellsPopulation of cellsSingle-cell transcriptomic dataSingle cellsCell cycle signatureTranscriptome dataCellular statesRNA sequencingCell cycleExpression profilesCell typesTranscriptomePublished datasetsCaptured cellsCustomized predictorCellsComputational approachSupervised machine learning methodsMachine learning methodsNormalisation strategyComputational assignmentLearning methodsPCA-based approachMolecular and neuronal homology between the olfactory systems of zebrafish and mouse
Saraiva L, Ahuja G, Ivandic I, Syed A, Marioni J, Korsching S, Logan D. Molecular and neuronal homology between the olfactory systems of zebrafish and mouse. Scientific Reports 2015, 5: 11487. PMID: 26108469, PMCID: PMC4480006, DOI: 10.1038/srep11487.Peer-Reviewed Original ResearchConceptsDegree of molecular conservationYears of evolutionary divergenceVomeronasal organOlfactory mucosaOlfactory organChemosensory receptor genesOlfactory systemTranscriptome of miceDual olfactory systemEvolutionary divergenceMolecular conservationNeuronal homologRepertoire sizeRNA abundanceMolecular relationshipsCell-specific markersClasses of neuronsMolecular basisChemosensory receptorsMarker genesOrgans of rodentsAbsolute abundanceZebrafishReceptor geneVertebrates
2014
Olfactory Receptor Patterning in a Higher Primate
Horowitz L, Saraiva L, Kuang D, Yoon K, Buck L. Olfactory Receptor Patterning in a Higher Primate. Journal Of Neuroscience 2014, 34: 12241-12252. PMID: 25209267, PMCID: PMC4160765, DOI: 10.1523/jneurosci.1779-14.2014.Peer-Reviewed Original ResearchConceptsTrace amine-associated receptorsHuman trace amine-associated receptorDetect social cuesHuman olfactory perceptionOdorant receptorsMammalian olfactory systemOrganization of sensory inputsSocial cuesOlfactory perceptionOlfactory bulbOlfactory systemSensory inputInstinctive behaviorMouse nosePrimatesDifferent domainsOrganizational strategiesReceptor patternsMacaquesReceptorsCuesChemosensory receptorsMiceOlfactionBrainThe Olfactory Transcriptomes of Mice
Ibarra-Soria X, Levitin M, Saraiva L, Logan D. The Olfactory Transcriptomes of Mice. PLOS Genetics 2014, 10: e1004593. PMID: 25187969, PMCID: PMC4154679, DOI: 10.1371/journal.pgen.1004593.Peer-Reviewed Original ResearchConceptsVomeronasal receptorsVR genesProtein-coding genesProtein coding sequencesDeep RNA sequencingDistribution of abundanceEvidence of expressionCell-specific expressionReference genomeGene annotationMultiple malesMulti-exonQuantitative catalogOlfactory tissueMouse genomeCoding sequenceOR genesOlfactory-mediated behaviorsGenomic techniquesExpression microarraysRNA sequencingGene expressionGenesQuantitative RT-PCRSexual dimorphism