2021
TNF stimulation primarily modulates transcriptional burst size of NF‐κB‐regulated genes
Bass VL, Wong VC, Bullock ME, Gaudet S, Miller‐Jensen K. TNF stimulation primarily modulates transcriptional burst size of NF‐κB‐regulated genes. Molecular Systems Biology 2021, 17: msb202010127. PMID: 34288498, PMCID: PMC8290835, DOI: 10.15252/msb.202010127.Peer-Reviewed Original ResearchConceptsNF-κB-regulated inflammatory genesGene expression noiseOpen chromatin environmentTranscriptional burst sizeNF-κB target genesNF-κB-regulated genesHistone 3 acetylationChromatin environmentTranscription factor NF-κBTranscriptional noiseExpression noiseTranscriptional burstingTranscript distributionFactor NF-κBGene promoterSubset of cellsIntercellular heterogeneityTNF stimulationCell heterogeneityGenesTNF protein expressionTNF activationProtein expressionTranscriptionBurst sizeCo-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