2024
Gene trajectory inference for single-cell data by optimal transport metrics
Qu R, Cheng X, Sefik E, Stanley III J, Landa B, Strino F, Platt S, Garritano J, Odell I, Coifman R, Flavell R, Myung P, Kluger Y. Gene trajectory inference for single-cell data by optimal transport metrics. Nature Biotechnology 2024, 1-11. PMID: 38580861, PMCID: PMC11452571, DOI: 10.1038/s41587-024-02186-3.Peer-Reviewed Original ResearchGene dynamicsGene programTrajectory inferenceBiological processesCell-cell graphDynamics of genesCell trajectory inferenceSingle-cell RNA sequencingSingle-cell dataCell state transitionsMyeloid lineage maturationDynamics of biological processesGene distributionRNA sequencingPseudotemporal orderingGene processingTrajectories of cellsGenesActivity of biological processesTechnical noiseGroups of cellsLineage maturationCellsConstruct cellsSequence
2023
Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions
Kaffe E, Roulis M, Zhao J, Qu R, Sefik E, Mirza H, Zhou J, Zheng Y, Charkoftaki G, Vasiliou V, Vatner D, Mehal W, AlcHepNet, Kluger Y, Flavell R. Humanized mouse liver reveals endothelial control of essential hepatic metabolic functions. Cell 2023, 186: 3793-3809.e26. PMID: 37562401, PMCID: PMC10544749, DOI: 10.1016/j.cell.2023.07.017.Peer-Reviewed Original ResearchConceptsMetabolic functionsSpecies-specific interactionsKey metabolic functionsCell-autonomous mechanismsNon-alcoholic fatty liver diseaseMajor metabolic hubNon-parenchymal cellsMetabolic hubHuman hepatocytesMicroenvironmental regulationHuman diseasesHuman-specific aspectsHuman pathologiesHomeostatic processesSpecies mismatchCholesterol uptakeFatty liver diseaseParacrine mannerHuman immuneBile acid conjugationSinusoidal endothelial cellsHepatic metabolic functionMouse liverEndothelial cellsCells
2021
Detection of differentially abundant cell subpopulations in scRNA-seq data
Zhao J, Jaffe A, Li H, Lindenbaum O, Sefik E, Jackson R, Cheng X, Flavell RA, Kluger Y. Detection of differentially abundant cell subpopulations in scRNA-seq data. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2100293118. PMID: 34001664, PMCID: PMC8179149, DOI: 10.1073/pnas.2100293118.Peer-Reviewed Original ResearchMeSH KeywordsAgingB-LymphocytesBrainCell LineageCOVID-19CytokinesDatasets as TopicDendritic CellsGene Expression ProfilingGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansMelanomaMonocytesPhenotypeRNA, Small CytoplasmicSARS-CoV-2Severity of Illness IndexSingle-Cell AnalysisSkin NeoplasmsT-LymphocytesTranscriptomeConceptsDA subpopulationsIll COVID-19 patientsImmune checkpoint therapyCOVID-19 patientsSingle-cell RNA sequencing analysisCheckpoint therapyBrain tissueCell subpopulationsRNA sequencing analysisTime pointsSubpopulationsDiseased individualsDistinct phenotypesOriginal studyCell typesAbundant subpopulationSequencing analysisCellsDA measuresPhenotypeImportant differencesNonrespondersPatientsTherapy
2020
Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses
Low JS, Farsakoglu Y, Vesely M, Sefik E, Kelly JB, Harman CCD, Jackson R, Shyer JA, Jiang X, Cauley LS, Flavell RA, Kaech SM. Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses. Journal Of Experimental Medicine 2020, 217: e20192291. PMID: 32525985, PMCID: PMC7398161, DOI: 10.1084/jem.20192291.Peer-Reviewed Original ResearchConceptsMemory T cellsT cellsLung CD8TRM cellsTissue-resident memory T cellsLong-term protective immunityT cell reactivationCell reactivationPortal of infectionCell functional responsesMemory CD8Protective immunityEffector responsesLymphoid organsCD8Distinct functional responsesFunctional responseReactivationCellsAPCActivation kineticsCritical roleResponseInfectionImmunity
2015
Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells
Sefik E, Geva-Zatorsky N, Oh S, Konnikova L, Zemmour D, McGuire AM, Burzyn D, Ortiz-Lopez A, Lobera M, Yang J, Ghosh S, Earl A, Snapper SB, Jupp R, Kasper D, Mathis D, Benoist C. Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells. Science 2015, 349: 993-997. PMID: 26272906, PMCID: PMC4700932, DOI: 10.1126/science.aaa9420.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteriaBacteroidetesColitis, UlcerativeColonForkhead Transcription FactorsHomeostasisHumansImmunity, MucosalIntestinal MucosaMice, Inbred C57BLMicrobiotaNuclear Receptor Subfamily 1, Group F, Member 3SymbiosisTh17 CellsT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryTranscription, GeneticTranscriptomeConceptsRegulatory T cellsImmuno-inflammatory responseT helper 17 (Th17) cell differentiationTranscription factor Foxp3Important effector moleculeRegulatory cellsHuman gut microbiotaFactor Foxp3T cellsRelated cell typesGut microbiotaMouse colonRORγSymbiotic membersIntestinal symbiontsFoxp3Tissue homeostasisEffector moleculesCell differentiationCell typesDistinct populationsCellsDifferent outcomesInflammation
2014
Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut
Morton A, Sefik E, Upadhyay R, Weissleder R, Benoist C, Mathis D. Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 6696-6701. PMID: 24753589, PMCID: PMC4020091, DOI: 10.1073/pnas.1405634111.Peer-Reviewed Original ResearchConceptsIntestinal microbiotaKaede transgenic miceFluorescent reportersIntestinal leukocytesFilamentous bacteriaGutMyeloid populationsK/BxN miceTh17 cellsEndoscopic approachImmune cellsLeukocyte subsetsAutoinflammatory diseasesImmune homeostasisDescending colonTransgenic miceLeukocyte movementLeukocytesMounting evidenceCellsMiceMicrobiotaTraffickingBacteria