2024
RORγt up-regulates RAG gene expression in DP thymocytes to expand the Tcra repertoire
Naik A, Dauphars D, Corbett E, Simpson L, Schatz D, Krangel M. RORγt up-regulates RAG gene expression in DP thymocytes to expand the Tcra repertoire. Science Immunology 2024, 9: eadh5318. PMID: 38489350, PMCID: PMC11005092, DOI: 10.1126/sciimmunol.adh5318.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGene ExpressionMiceNuclear Receptor Subfamily 1, Group F, Member 3Receptors, Antigen, T-Cell, alpha-betaThymocytesTranscription FactorsConceptsRecombination activating geneDP thymocytesUp-regulatedAntigen receptor lociDouble-positive (DP) stageRAG expressionTranscriptional up-regulationDouble-negative (DNRAG gene expressionActive genesTcra repertoireReceptor locusDN thymocytesGene expressionThymocyte transitionLymphocyte developmentThymocyte proliferationPhysiological importanceMultiple pathwaysRORgtThymocytesExpressionRepertoireRecombinationAntisilencing
2016
Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies
Brauer PM, Pessach IM, Clarke E, Rowe JH, Ott de Bruin L, Lee YN, Dominguez-Brauer C, Comeau AM, Awong G, Felgentreff K, Zhang YH, Bredemeyer A, Al-Herz W, Du L, Ververs F, Kennedy M, Giliani S, Keller G, Sleckman BP, Schatz DG, Bushman FD, Notarangelo LD, Zúñiga-Pflücker JC. Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies. Blood 2016, 128: 783-793. PMID: 27301863, PMCID: PMC4982452, DOI: 10.1182/blood-2015-10-676304.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDNA BreaksGenes, RAG-1Homeodomain ProteinsHumansInduced Pluripotent Stem CellsInfantMutationReceptors, Antigen, T-Cell, alpha-betaSevere Combined ImmunodeficiencyT-LymphocytesV(D)J RecombinationConceptsInduced pluripotent stem cellsT cell developmentPluripotent stem cellsT cell receptorStem cellsOmenn syndrome patientsSingle-strand DNA breaksHuman induced pluripotent stem cellsControl iPSCsDeep-sequencing analysisT lineage cellsHuman T-cell developmentT cell progenitorsIPSC-derived cellsJoining genesImpaired T-cell differentiationDNA breaksSame geneN-terminalImmune system developmentLocus rearrangementT cell differentiationPatient cellsRecombination activityGenetic defects
2013
Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2
Chan EA, Teng G, Corbett E, Choudhury KR, Bassing CH, Schatz DG, Krangel MS. Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: e4628-e4637. PMID: 24218622, PMCID: PMC3845165, DOI: 10.1073/pnas.1310846110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell NucleusDNA-Binding ProteinsImage Processing, Computer-AssistedIn Situ Hybridization, FluorescenceMiceMice, KnockoutMicroscopy, ConfocalReceptors, Antigen, T-Cell, alpha-betaRecombination, GeneticConceptsTcrb allelesNuclear peripheryNuclear laminaDNA repair protein 53BP1RNA polymerase IIGene 2 proteinHistone H3K4 trimethylationPericentromeric heterochromatinPolymerase IIH3K4 trimethylationRAG proteinsProtein 53BP1Subnuclear distributionRecombination eventsAllelic exclusionDouble-negative thymocytesT-cell receptor βHigher-Order Looping and Nuclear Organization of Tcra Facilitate Targeted RAG Cleavage and Regulated Rearrangement in Recombination Centers
Chaumeil J, Micsinai M, Ntziachristos P, Deriano L, Wang J, Ji Y, Nora EP, Rodesch MJ, Jeddeloh JA, Aifantis I, Kluger Y, Schatz DG, Skok JA. Higher-Order Looping and Nuclear Organization of Tcra Facilitate Targeted RAG Cleavage and Regulated Rearrangement in Recombination Centers. Cell Reports 2013, 3: 359-370. PMID: 23416051, PMCID: PMC3664546, DOI: 10.1016/j.celrep.2013.01.024.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell NucleusDNA DamageDNA-Binding ProteinsGenetic LociGenomic InstabilityHistonesHomeodomain ProteinsMiceMice, Inbred C57BLMice, Inbred CBAMice, KnockoutProtein Serine-Threonine KinasesReceptors, Antigen, T-Cell, alpha-betaTumor Suppressor ProteinsV(D)J RecombinationConceptsAntigen receptor lociRegulated rearrangementsGenome stabilityNuclear organizationRAG cleavageRAG recombinaseNuclear accessibilityRAG bindingCellular transformationΑ locusRecombination eventsReceptor locusDiverse arrayCell receptorLociLoop formationTight controlRegulationCleavageFocal bindingGenetic anomaliesBindingKey determinantRearrangementTranscription
2011
A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation
Seitan VC, Hao B, Tachibana-Konwalski K, Lavagnolli T, Mira-Bontenbal H, Brown KE, Teng G, Carroll T, Terry A, Horan K, Marks H, Adams DJ, Schatz DG, Aragon L, Fisher AG, Krangel MS, Nasmyth K, Merkenschlager M. A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation. Nature 2011, 476: 467-471. PMID: 21832993, PMCID: PMC3179485, DOI: 10.1038/nature10312.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCell DifferentiationChromosomal Proteins, Non-HistoneDNA-Binding ProteinsGene Expression RegulationGene Rearrangement, T-LymphocyteGenes, RAG-1MiceNuclear ProteinsPhosphoproteinsReceptors, Antigen, T-Cell, alpha-betaRecombinasesThymus GlandTranscription, Genetic
2010
Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination
Ji Y, Little AJ, Banerjee JK, Hao B, Oltz EM, Krangel MS, Schatz DG. Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination. Journal Of Experimental Medicine 2010, 207: 2809-2816. PMID: 21115692, PMCID: PMC3005232, DOI: 10.1084/jem.20101136.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsBinding, CompetitiveChromatin ImmunoprecipitationDNAEnhancer Elements, GeneticFemaleGene RearrangementGenes, ImmunoglobulinGenotypeHistonesHMGB1 ProteinHomeodomain ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticProtein BindingReceptors, Antigen, T-Cell, alpha-betaRecombination, GeneticTranscription, GeneticVDJ Recombinases
1999
Distinct effects of Jak3 signaling on alphabeta and gammadelta thymocyte development.
Eynon E, Livák F, Kuida K, Schatz D, Flavell R. Distinct effects of Jak3 signaling on alphabeta and gammadelta thymocyte development. The Journal Of Immunology 1999, 162: 1448-59. PMID: 9973401, DOI: 10.4049/jimmunol.162.3.1448.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell DivisionCell SurvivalGene ExpressionGene Rearrangement, delta-Chain T-Cell Antigen ReceptorGene Rearrangement, gamma-Chain T-Cell Antigen ReceptorGenes, bcl-2Janus Kinase 3MiceMice, Inbred C57BLMice, KnockoutMice, TransgenicProtein-Tyrosine KinasesReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaSignal TransductionT-Lymphocyte SubsetsConceptsJak3-/- miceGammadelta T cell lineagesThymocyte developmentTransduction of signalsTCRbeta chain gene rearrangementLineage differentiationGammadelta lineageCell lineagesGene resultsKinase 3Developmental blockadeEarly thymocyte differentiationCytokine receptorsGamma locusT-cell lineageTargeted deletionBcl-2 expressionThymocyte differentiationTCRbeta transgeneIL-2 familyLineagesDifferentiationImmature thymocytesTransgeneSevere reduction
1997
αβ Lineage‐committed thymocytes can be rescued by the γδ T cell receptor (TCR) in the absence of TCR β chain
Livák F, Wilson A, MacDonald H, Schatz D. αβ Lineage‐committed thymocytes can be rescued by the γδ T cell receptor (TCR) in the absence of TCR β chain. European Journal Of Immunology 1997, 27: 2948-2958. PMID: 9394823, DOI: 10.1002/eji.1830271130.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationFemaleGene Expression RegulationGene Rearrangement, alpha-Chain T-Cell Antigen ReceptorMiceMice, Inbred AKRMice, Inbred C57BLMice, KnockoutMice, TransgenicModels, ImmunologicalReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaT-Lymphocyte SubsetsThymus GlandTransgenesConceptsT cell receptorLineage commitmentT cell lineage commitmentCell lineage commitmentAlpha beta T cell developmentTCR beta proteinGamma delta T cell lineagesAlpha beta lineageT cell developmentCell receptorTCR-mediated selectionGene rearrangementsCell lineagesT cellsΑβ lineageCell developmentTCR gammaAlpha betaT-cell lineageBeta lineageLineagesGamma delta T-cell receptorTCR β chainGamma delta T cellsDelta T-cell receptor
1996
Productive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo.
Hoffman ES, Passoni L, Crompton T, Leu TM, Schatz DG, Koff A, Owen MJ, Hayday AC. Productive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo. Genes & Development 1996, 10: 948-962. PMID: 8608942, DOI: 10.1101/gad.10.8.948.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, T-LymphocyteCell CycleCell SeparationClone CellsCyclinsDNA-Binding ProteinsFemaleFlow CytometryFluorescent Antibody Technique, IndirectGene Expression Regulation, DevelopmentalGene Rearrangement, beta-Chain T-Cell Antigen ReceptorHomeodomain ProteinsHyaluronan ReceptorsMiceMice, Inbred C57BLProteinsReceptors, Antigen, T-Cell, alpha-betaReceptors, Interleukin-2Retinoblastoma ProteinRNA, MessengerT-LymphocytesThymus GlandConceptsTCRbeta chain genesBeta selectionT-cell receptor beta-chain locusChain geneTCRbeta chain gene rearrangementAlpha beta T cell developmentProductive gene rearrangementHyperphosphorylation of RbGene rearrangementsTCR gene rearrangementsTransition of thymocytesTCRbeta gene rearrangementT cell developmentRegulation of p27Coincident regulationBeta-chain locusPopulation of cellsTCR lociCell cycleCdc2 activityCDK2 activityTCRbeta selectionCyclin AThymocyte expansionCell phenotypeT-Cell Receptor α Locus V(D)J Recombination By-Products Are Abundant in Thymocytes and Mature T Cells
Livak F, Schatz D. T-Cell Receptor α Locus V(D)J Recombination By-Products Are Abundant in Thymocytes and Mature T Cells. Molecular And Cellular Biology 1996, 16: 609-618. PMID: 8552089, PMCID: PMC231040, DOI: 10.1128/mcb.16.2.609.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceDNA DamageGene Rearrangement, alpha-Chain T-Cell Antigen ReceptorImmune SystemMiceMice, Inbred C57BLMolecular Probe TechniquesMolecular Sequence DataReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaRecombination, GeneticT-LymphocytesThymus GlandConceptsRecombination signal sequencesSignal sequenceDNA moleculesAlpha locusTCR alpha/delta locusAlpha/delta locusBroken DNA moleculesReciprocal productsJ alpha locusTermination of expressionT-cell receptor α locusC delta regionTCR alpha locusSouthern blot analysisT cell developmentGenome integrityDNA existΑ locusQuantitative Southern blot analysisT-cell receptor genesCoding regionsDevelopmental transitionsLymphoid developmentDelta locusRAG-2
1995
In-frame TCR δ gene rearrangements play a critical role in the αβ/γδ T cell lineage decision
Livak F, Petrie H, Crisps I, Schatz D. In-frame TCR δ gene rearrangements play a critical role in the αβ/γδ T cell lineage decision. Immunity 1995, 2: 617-627. PMID: 7796295, DOI: 10.1016/1074-7613(95)90006-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell DifferentiationFemaleGene Rearrangement, T-LymphocyteMiceMice, Inbred AKRMice, Inbred C57BLMolecular Sequence DataReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaT-LymphocytesConceptsT cell lineage decisionsCell lineage decisionsLineage decisionsRandom gene rearrangementsSouthern blot analysisT cell receptor complexCell receptor complexGene rearrangementsDelta locusLocus sequenceGamma delta lineageReceptor complexT cell receptorBlot analysisDistinct precursorsCommon precursorCell receptorCritical roleDelta rearrangementsDelta lineageRearrangementΔ gene rearrangementAlpha betaT cellsGamma delta T-cell receptor
1993
Multiple rearrangements in T cell receptor alpha chain genes maximize the production of useful thymocytes.
Petrie HT, Livak F, Schatz DG, Strasser A, Crispe IN, Shortman K. Multiple rearrangements in T cell receptor alpha chain genes maximize the production of useful thymocytes. Journal Of Experimental Medicine 1993, 178: 615-622. PMID: 8393478, PMCID: PMC2191132, DOI: 10.1084/jem.178.2.615.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD3 ComplexCell DivisionCells, CulturedGene Rearrangement, alpha-Chain T-Cell Antigen ReceptorHomeodomain ProteinsMiceMice, Inbred C57BLMice, TransgenicProteinsReceptors, Antigen, T-Cell, alpha-betaThymus GlandConceptsAlpha/beta heterodimerMultiple rearrangementsTCR alpha/beta heterodimerBeta heterodimerBeta chainT-cell receptor alpha-chain geneChain geneTCR alpha geneTCR alphaSurface expressionReceptor alpha-chain geneTransgenic TCR beta chainTCR alpha locusAlpha chain geneT cell receptor alphaAlpha gene rearrangementsMajority of TCREndogenous TCR alpha chainsHeavy chain genePositive selectionSomatic rearrangementsAllelic exclusionAlpha geneAlpha locusTCR alpha chain