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
2016
Redefining Signaling Pathways with an Expanding Single-Cell Toolbox
Gaudet S, Miller-Jensen K. Redefining Signaling Pathways with an Expanding Single-Cell Toolbox. Trends In Biotechnology 2016, 34: 458-469. PMID: 26968612, PMCID: PMC4958913, DOI: 10.1016/j.tibtech.2016.02.009.Peer-Reviewed Original ResearchConceptsSignaling pathwaysSingle-cell toolsDNA damage responseCanonical signaling pathwaysSingle-cell measurementsNovel mechanistic insightsCell variabilityStress responseBiological informationAnalytical pipelineEnvironmental stimuliImaging-based approachIdentical cellsCell proliferationMechanistic insightsSingle cellsRecent technological advancesPathwayCellsUnderlying mechanismVivo applicabilityCell responsesResponseProliferationCell measurements
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 ResearchConceptsSingle 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
2013
High-Throughput Secretomic Analysis of Single Cells to Assess Functional Cellular Heterogeneity
Lu Y, Chen JJ, Mu L, Xue Q, Wu Y, Wu PH, Li J, Vortmeyer AO, Miller-Jensen K, Wirtz D, Fan R. High-Throughput Secretomic Analysis of Single Cells to Assess Functional Cellular Heterogeneity. Analytical Chemistry 2013, 85: 2548-2556. PMID: 23339603, PMCID: PMC3589817, DOI: 10.1021/ac400082e.Peer-Reviewed Original ResearchConceptsCellular functionsSingle cellsCellular heterogeneityArray of proteinsMultiplexed protein detectionSecreted proteinsSecretomic analysisLow sample consumptionComplex biological samplesProtein secretionIndividual cellsPrimary cellsProtein detectionAssay platformHigh throughputCell linesSample consumptionStandardized data analysisEase of operationProteinBiological samplesCellsHuman healthInformative monitoringDistinct heterogeneity