2023
Reframing macrophage diversity with network motifs
Pizzurro G, Miller-Jensen K. Reframing macrophage diversity with network motifs. Trends In Immunology 2023, 44: 965-970. PMID: 37949786, PMCID: PMC11057955, DOI: 10.1016/j.it.2023.10.009.Commentaries, Editorials and LettersConceptsNetwork motifsDistinct biological functionsSystems biology conceptsMacrophage stateMacrophage responseBiological functionsMacrophage diversityExtracellular networkMacrophage activationDisease contextsMotifLocal molecular interactionsMolecular interactionsFunctional modulesBiology conceptsDiversityActivationTissueIntracellularResponse
2021
Single-cell secretion analysis reveals a dual role for IL-10 in restraining and resolving the TLR4-induced inflammatory response
Alexander AF, Kelsey I, Forbes H, Miller-Jensen K. Single-cell secretion analysis reveals a dual role for IL-10 in restraining and resolving the TLR4-induced inflammatory response. Cell Reports 2021, 36: 109728. PMID: 34551303, PMCID: PMC8995750, DOI: 10.1016/j.celrep.2021.109728.Peer-Reviewed Original ResearchCo-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells
Muñoz-Rojas AR, Kelsey I, Pappalardo JL, Chen M, Miller-Jensen K. Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells. Nature Communications 2021, 12: 301. PMID: 33436596, PMCID: PMC7804107, DOI: 10.1038/s41467-020-20540-2.Peer-Reviewed Original ResearchConceptsCo-stimulated macrophagesFunctional diversitySingle-cell RNA sequencingGlobal transcriptional programSuch functional diversityTranscriptional programsTissue homeostasisRNA sequencingEnvironmental cuesGene resultsExclusive expressionInflammatory stimuli LPSCell heterogeneityIndividual cellsPolarization cuesIndividual macrophagesTissue repairCytokine genesDiversityInnate immune cellsFighting infectionsCellsMacrophagesCuesTranscription
2019
Microfluidic platform enables live-cell imaging of signaling and transcription combined with multiplexed secretion measurements in the same single cells
Ramji R, Alexander AF, Muñoz-Rojas AR, Kellman LN, Miller-Jensen K. Microfluidic platform enables live-cell imaging of signaling and transcription combined with multiplexed secretion measurements in the same single cells. Integrative Biology 2019, 11: 142-153. PMID: 31242304, PMCID: PMC8672722, DOI: 10.1093/intbio/zyz013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesCell CommunicationChemokine CCL2Chemokine CCL3Chemokine CCL5Equipment DesignLab-On-A-Chip DevicesLipopolysaccharidesMacrophagesMiceMice, Inbred C57BLMicrofluidicsRAW 264.7 CellsSignal TransductionTranscription Factor RelATranscription, GeneticTumor Necrosis Factor-alphaConceptsLive-cell imagingCell variabilitySame single cellSingle-cell assaysTranscription dynamicsBacterial component lipopolysaccharideDownstream responsesPathogenic assaultFluorescent reportersProtein secretionSingle cellsCell processesBiological sourcesCCL3 secretionRelative levelsCellsInnate immune cellsTranslocation dynamicsBiological stepC secretionTranscriptionSecretionCCL5 secretionRelAReporter
2018
Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair
Shook BA, Wasko RR, Rivera-Gonzalez GC, Salazar-Gatzimas E, López-Giráldez F, Dash BC, Muñoz-Rojas AR, Aultman KD, Zwick RK, Lei V, Arbiser JL, Miller-Jensen K, Clark DA, Hsia HC, Horsley V. Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair. Science 2018, 362 PMID: 30467144, PMCID: PMC6684198, DOI: 10.1126/science.aar2971.Peer-Reviewed Original ResearchConceptsDifferential gene expressionAdipocyte precursorsExtracellular matrix moleculesGene expressionTransplantation assaysMatrix moleculesFactor C.Factor 1Insulin-like growth factor-1Cell populationsTissue resilienceDistinct subpopulationsGrowth factor-1Profibrotic cellsTissue repairMultiple mouse modelsECM depositionSkin repairTissue dysfunctionProliferationMouse modelMyofibroblastsWoundingMacrophagesRepairMyeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity
Perry CJ, Muñoz-Rojas AR, Meeth KM, Kellman LN, Amezquita RA, Thakral D, Du VY, Wang JX, Damsky W, Kuhlmann AL, Sher JW, Bosenberg M, Miller-Jensen K, Kaech SM. Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity. Journal Of Experimental Medicine 2018, 215: 877-893. PMID: 29436395, PMCID: PMC5839759, DOI: 10.1084/jem.20171435.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD40 AntigensCell ProliferationImmunotherapyInflammationInterferon-gammaMacrophagesMelanoma, ExperimentalMiceMyeloid CellsNeoplasmsPhenotypeProto-Oncogene Proteins B-rafPTEN PhosphohydrolaseReceptors, Granulocyte-Macrophage Colony-Stimulating FactorRNA, MessengerSurvival AnalysisT-LymphocytesTranscription, GeneticTumor Necrosis Factor-alphaConceptsCombination therapyEffective antitumor immune responseProtective T cell responsesTumor-associated myeloid cellsM2-like stateCheckpoint inhibitor therapyAntitumor immune responseT cell responsesCSF-1R inhibitorAntitumor immunityInhibitor therapySuch patientsIL-12IL-6Cancer immunotherapyTAM subsetsUntreated tumorsT cellsImmune responseMouse modelTherapeutic targetTAM subpopulationsMyeloid cellsTumor growthCell responses
2016
Distinct Signaling Thresholds Distinguish Friend from Foe
Miller-Jensen K. Distinct Signaling Thresholds Distinguish Friend from Foe. Cell Systems 2016, 2: 360-361. PMID: 27336965, DOI: 10.1016/j.cels.2016.06.003.Peer-Reviewed Original Research
2015
Analysis of single-cell cytokine secretion reveals a role for paracrine signaling in coordinating macrophage responses to TLR4 stimulation
Xue Q, Lu Y, Eisele MR, Sulistijo ES, Khan N, Fan R, Miller-Jensen K. Analysis of single-cell cytokine secretion reveals a role for paracrine signaling in coordinating macrophage responses to TLR4 stimulation. Science Signaling 2015, 8: ra59. PMID: 26082435, PMCID: PMC5735825, DOI: 10.1126/scisignal.aaa2155.Peer-Reviewed Original ResearchConceptsGraphical Gaussian modelingMonocyte-derived macrophagesSingle-cell dataMacrophage-like U937 cellsCell populationsHuman monocyte-derived macrophagesRegulatory networksUncharacterized roleCell communicationInnate immune responseParacrine signalsCell heterogeneityCytokine secretionRole of paracrineU937 cellsMultiple cytokinesSingle cellsGGM networkToll-like receptor 4ParacrineSmall subpopulationMacrophage responseCellsRapid innate immune responseCell isolationHighly multiplexed profiling of single-cell effector functions reveals deep functional heterogeneity in response to pathogenic ligands
Lu Y, Xue Q, Eisele MR, Sulistijo ES, Brower K, Han L, Amir el-AD, Pe'er D, Miller-Jensen K, Fan R. Highly multiplexed profiling of single-cell effector functions reveals deep functional heterogeneity in response to pathogenic ligands. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e607-e615. PMID: 25646488, PMCID: PMC4343126, DOI: 10.1073/pnas.1416756112.Peer-Reviewed Original ResearchMeSH KeywordsHumansLigandsLipopolysaccharidesMacrophagesSingle-Cell AnalysisToll-Like Receptor 4U937 CellsVirulenceConceptsSingle cellsSingle-cell genomicsSame single cellImmune effector proteinsFunctional heterogeneityToll-like receptor 4Similar cell populationsMacrophage inhibitory factorEffector proteinsCell activation processProtein profilingPopulation ArchitectureMultiplexed profilingFunctional stateDifferentiated macrophagesPrimary macrophagesCell populationsSecretion assaysPathogenic ligandsDifferent cytokine profilesProfilingPathogenic activationProteinActivation of lipopolysaccharideCells