2024
Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development
Wu H, Saito-Diaz K, Huang C, McAlpine J, Seo D, Magruder D, Ishan M, Bergeron H, Delaney W, Santori F, Krishnaswamy S, Hart G, Chen Y, Hogan R, Liu H, Ivanova N, Zeltner N. Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development. Cell Stem Cell 2024, 31: 734-753.e8. PMID: 38608707, PMCID: PMC11069445, DOI: 10.1016/j.stem.2024.03.011.Peer-Reviewed Original ResearchConceptsAutonomic nervous systemSjogren's syndromeParasympathetic neuronsFamilial dysautonomiaWhite adipocytesAutoimmune disease Sjogren's syndromeHuman pluripotent stem cellsHuman pluripotent stem cell (hPSC)-derived neuronsHuman developmental studiesPluripotent stem cellsSARS-CoV-2 infectionSchwann cell progenitorsAutonomic neuropathyCell progenitorsStem cellsModel systemNervous systemSARS-CoV-2Human diseasesDysfunctionNeuronsDifferentiation paradigmOrgan developmentNeuropathyDrug discovery studies
2023
PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens
Damo M, Hornick N, Venkat A, William I, Clulo K, Venkatesan S, He J, Fagerberg E, Loza J, Kwok D, Tal A, Buck J, Cui C, Singh J, Damsky W, Leventhal J, Krishnaswamy S, Joshi N. PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens. Nature 2023, 619: 151-159. PMID: 37344588, PMCID: PMC10989189, DOI: 10.1038/s41586-023-06217-y.Peer-Reviewed Original ResearchConceptsEffector CD8 T cellsCD8 T cellsAntigen-specific effector CD8 T cellsAntigen-specific CD8 T cellsAntigen-expressing cellsT cell tolerancePD-1T cellsAdverse eventsCell toleranceCD8 T cell toleranceImmune-related adverse eventsPeripheral T cell repertoirePeripheral T cell toleranceNon-lesional skinT cell repertoireT-cell antigensPeripheral toleranceCheckpoint receptorsSkin biopsiesLocal infiltrationLocal pathologyCell repertoireMouse modelSkin tolerancelinc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells
Tornini V, Miao L, Lee H, Gerson T, Dube S, Schmidt V, Kroll F, Tang Y, Du K, Kuchroo M, Vejnar C, Bazzini A, Krishnaswamy S, Rihel J, Giraldez A. linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells. ELife 2023, 12: e82249. PMID: 37191016, PMCID: PMC10188112, DOI: 10.7554/elife.82249.Peer-Reviewed Original ResearchConceptsCell typesIntergenic non-coding RNAsChromatin architectural proteinCryptic open reading frameGene regulatory networksOpen reading frameNon-coding RNAsNew cell typesNeural cell typesBrain cell typesPutative lincRNAsVertebrate genomesArchitectural proteinsChromatin disruptionChromatin accessibilityRegulatory networksGenetic basisCell developmentMicropeptidesBrain cell developmentReceptor-mediated pathwaySystematic identificationLincRNAsNeural cellsCerebellar cellsSingle-cell analysis reveals inflammatory interactions driving macular degeneration
Kuchroo M, DiStasio M, Song E, Calapkulu E, Zhang L, Ige M, Sheth A, Majdoubi A, Menon M, Tong A, Godavarthi A, Xing Y, Gigante S, Steach H, Huang J, Huguet G, Narain J, You K, Mourgkos G, Dhodapkar R, Hirn M, Rieck B, Wolf G, Krishnaswamy S, Hafler B. Single-cell analysis reveals inflammatory interactions driving macular degeneration. Nature Communications 2023, 14: 2589. PMID: 37147305, PMCID: PMC10162998, DOI: 10.1038/s41467-023-37025-7.Peer-Reviewed Original ResearchConceptsAge-related macular degenerationMacular degenerationNeurodegenerative diseasesNeurodegenerative conditionsLate-stage age-related macular degenerationPossible new therapeutic targetsPostmortem human retinaProgressive multiple sclerosisNew therapeutic targetsEarly phaseSingle-nucleus RNA sequencingInflammatory interactionsMultiple sclerosisInterleukin-1βDisease progressionControl retinasTherapeutic approachesGlial populationsGlial stateTherapeutic targetDisease pathogenesisRetinal diseasesAlzheimer's diseaseDiseaseHuman retinaCell cycle controls long-range calcium signaling in the regenerating epidermis
Moore J, Bhaskar D, Gao F, Matte-Martone C, Du S, Lathrop E, Ganesan S, Shao L, Norris R, Sanz N, Annusver K, Kasper M, Cox A, Hendry C, Rieck B, Krishnaswamy S, Greco V. Cell cycle controls long-range calcium signaling in the regenerating epidermis. Journal Of Cell Biology 2023, 222: e202302095. PMID: 37102999, PMCID: PMC10140546, DOI: 10.1083/jcb.202302095.Peer-Reviewed Original Research
2014
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