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
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 ResearchMeSH KeywordsCytokinesHumansLipopolysaccharidesMacrophagesParacrine CommunicationSignal TransductionToll-Like Receptor 4U937 CellsConceptsGraphical 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