2022
A transcriptional cycling model recapitulates chromatin-dependent features of noisy inducible transcription
Bullock ME, Moreno-Martinez N, Miller-Jensen K. A transcriptional cycling model recapitulates chromatin-dependent features of noisy inducible transcription. PLOS Computational Biology 2022, 18: e1010152. PMID: 36084132, PMCID: PMC9491597, DOI: 10.1371/journal.pcbi.1010152.Peer-Reviewed Original ResearchMeSH KeywordsChromatinHIV InfectionsHIV-1HumansNF-kappa BTranscription, GeneticTranscriptional ActivationVirus LatencyConceptsGene expression noiseExpression noiseTranscriptional burstingPromoter statesDifferent chromatin environmentsChromatin environmentChromatin statePause releaseTranscription factor NFChromatin accessibilityChromatin remodelingTranscriptional noiseChromatin locationsInducible transcriptionSubstantial phenotypic heterogeneityTranscriptional activationTranscription factorsTranscript distributionPolymerase complexTarget genesPolymerase bindingGene expressionPromoter activityViral activationBiological processes
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 secretionRelAReporterFold-Change Detection of NF-κB at Target Genes with Different Transcript Outputs
Wong VC, Mathew S, Ramji R, Gaudet S, Miller-Jensen K. Fold-Change Detection of NF-κB at Target Genes with Different Transcript Outputs. Biophysical Journal 2019, 116: 709-724. PMID: 30704857, PMCID: PMC6382958, DOI: 10.1016/j.bpj.2019.01.011.Peer-Reviewed Original ResearchConceptsFold-change detectionTarget genesTranscript outputStress-responsive gene transcriptionSingle-cell dataNF-κB target genesRelA nuclear translocationLive-cell imagingMicrofluidic cell-trapping deviceLow-abundance transcriptsTranscription factor nuclear factorNF-κBRNA FISHTranscriptional outputΚB motifTranscript abundanceGene transcriptionTranscriptionTranscript numbersCell trap deviceJurkat TCell typesGenesNF-κB signalingMultiple biological mechanisms
2018
Myeloid-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
2015
Distinct promoter activation mechanisms modulate noise-driven HIV gene expression
Chavali AK, Wong VC, Miller-Jensen K. Distinct promoter activation mechanisms modulate noise-driven HIV gene expression. Scientific Reports 2015, 5: 17661. PMID: 26666681, PMCID: PMC4678399, DOI: 10.1038/srep17661.Peer-Reviewed Original Research
2013
Genetic Selection for Context-Dependent Stochastic Phenotypes: Sp1 and TATA Mutations Increase Phenotypic Noise in HIV-1 Gene Expression
Miller-Jensen K, Skupsky R, Shah PS, Arkin AP, Schaffer DV. Genetic Selection for Context-Dependent Stochastic Phenotypes: Sp1 and TATA Mutations Increase Phenotypic Noise in HIV-1 Gene Expression. PLOS Computational Biology 2013, 9: e1003135. PMID: 23874178, PMCID: PMC3708878, DOI: 10.1371/journal.pcbi.1003135.Peer-Reviewed Original ResearchMeSH KeywordsHIV-1HumansIn Vitro TechniquesMutationPhenotypeSelection, GeneticSp1 Transcription FactorStochastic ProcessesTATA BoxTranscription, GeneticConceptsGenomic contextGene expressionSp1 mutationPromoter sequencesStochastic phenotypeEukaryotic gene expressionForward genetic screenBasal expressionHIV-1 gene expressionViral gene expressionCore promoter regionSingle-cell experimentsGene expression levelsGenetic screenHIV LTR promoterPhenotypic noiseAbsence of TatTranscription factorsPromoter elementsGenomic integrationPositive feedback loopGenetic elementsRelevant model systemPromoter regionGenetic selection
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