Single-cell mass cytometry of TCR signaling: Amplification of small initial differences results in low ERK activation in NOD mice
Mingueneau M, Krishnaswamy S, Spitzer MH, Bendall SC, Stone EL, Hedrick SM, Pe'er D, Mathis D, Nolan GP, Benoist C. Single-cell mass cytometry of TCR signaling: Amplification of small initial differences results in low ERK activation in NOD mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 16466-16471. PMID: 25362052, PMCID: PMC4246343, DOI: 10.1073/pnas.1419337111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 1Disease Models, AnimalEnzyme ActivationExtracellular Signal-Regulated MAP KinasesGenetic VariationI-kappa B ProteinsImmune ToleranceImmunity, CellularImmunologic Deficiency SyndromesImmunologic MemoryLymph NodesLymphopoiesisMaleMAP Kinase Signaling SystemMass SpectrometryMiceMice, Inbred C57BLMice, Inbred NODMice, KnockoutMitogen-Activated Protein Kinase 1NF-KappaB Inhibitor alphaPhosphorylationProtein Processing, Post-TranslationalReceptors, Antigen, T-CellSelf ToleranceSingle-Cell AnalysisThymus GlandConceptsT cellsT cell differentiationNOD T cellsERK activationNonobese diabetic (NOD) miceMemory T cellsKO T cellsMass cytometrySingle-cell mass cytometryNOD miceDiabetic miceB6 miceControl C57BL/6Small impairmentMicePrimary deficiencyTCR signalingPhosphorylation levelsLarge defectsTCR triggeringActivationLower ERK activationImpairmentCytometryCellsConditional density-based analysis of T cell signaling in single-cell data
Krishnaswamy S, Spitzer MH, Mingueneau M, Bendall SC, Litvin O, Stone E, Pe'er D, Nolan GP. Conditional density-based analysis of T cell signaling in single-cell data. Science 2014, 346: 1250689. PMID: 25342659, PMCID: PMC4334155, DOI: 10.1126/science.1250689.Peer-Reviewed Original ResearchConceptsSingle-cell dataMitogen-activated protein kinase ERK2High-dimensional single-cell technologiesProtein kinase ERK2Single-cell technologiesNaïve cellsKinase ERK2Protein speciesCellular circuitsCell variationMolecular circuitsProteinMass cytometryAbundanceCellsCell subtypesComputational approachERK2Computational methodsSpeciesPERKCascadeFunctionT cellsPS6