2022
Langerhans cells are essential components of the angiogenic niche during murine skin repair
Wasko R, Bridges K, Pannone R, Sidhu I, Xing Y, Naik S, Miller-Jensen K, Horsley V. Langerhans cells are essential components of the angiogenic niche during murine skin repair. Developmental Cell 2022, 57: 2699-2713.e5. PMID: 36493773, PMCID: PMC10848275, DOI: 10.1016/j.devcel.2022.11.012.Peer-Reviewed Original ResearchConceptsAngiogenic nicheSingle-cell RNA sequencingLangerhans cellsControl of angiogenesisCanonical roleMouse geneticsPre-existing vesselsRNA sequencingImmune cellsSkin repairFunction of LCSkin-resident immune cellsNew blood vesselsMouse skin woundsThree-dimensional microscopyNicheNon-healing woundsEndothelial cellsAngiogenesisCellsCell immunityTreatment optionsInflammatory diseasesAntigen presentationInjury repair
2021
Co-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
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
2012
Systems biology of virus-host signaling network interactions
Xue Q, Miller-Jensen K. Systems biology of virus-host signaling network interactions. BMB Reports 2012, 45: 213-220. PMID: 22531130, DOI: 10.5483/bmbrep.2012.45.4.213.Peer-Reviewed Original ResearchConceptsVirus-host protein interactionsHost cell machineryHost protein targetsSystems biology approachVirus-mediated changesBiology approachCell machineryProtein interactionsCell variabilityViral perturbationsSystems biologyBiological contextHost cellsMolecular studiesNovel therapeutic targetIndividual pathwaysViral pathogenesisNew therapeutic strategiesTherapeutic targetComputational analysisVirus propagationHostHost responseCellsRecent advances
2011
Varying virulence: epigenetic control of expression noise and disease processes
Miller-Jensen K, Dey SS, Schaffer DV, Arkin AP. Varying virulence: epigenetic control of expression noise and disease processes. Trends In Biotechnology 2011, 29: 517-525. PMID: 21700350, DOI: 10.1016/j.tibtech.2011.05.004.Peer-Reviewed Original ResearchConceptsGene expression noiseExpression noisePhenotypic heterogeneityChromatin modificationsChromatin remodelingTranscriptional burstsEpigenetic controlReversible drug resistancePhenotypic diversityGene statesIdentical populationsDiseased cellsDrug resistanceCellsEukaryotesFundamental informationViral infectionVirulenceDiversityTherapeutic interventionsBetter understandingIntrinsic noiseRemodelingHeterogeneityRandom transitions
2007
Common effector processing mediates cell-specific responses to stimuli
Miller-Jensen K, Janes KA, Brugge JS, Lauffenburger DA. Common effector processing mediates cell-specific responses to stimuli. Nature 2007, 448: 604-608. PMID: 17637676, DOI: 10.1038/nature06001.Peer-Reviewed Original ResearchConceptsDistinct epithelial cell linesCell type-specific signalsCell type-specific outcomesCell specificityCell-specific responsesDifferent cell typesOrganismal homeostasisEmbryonic developmentEpithelial cell lineCommon effectorCell typesSpecific signalsMost cellsCell linesOrganismsEffectorsHomeostasisPathwaySpecificityCellsTherapeuticsEnigma